Search

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. more...

The sarcoplasmic (or endoplasmic) reticulum Ca2+-ATPase (SERCA)-3 has been implicated in the possible dysregulation of Ca2+ homeostasis that accompanies the pathology of hypertension and diabetes. We report the molecular cloning of two alternatively spliced transcripts from the human SERCA3 gene, ATP2A3, that encode proteins that differ at their carboxy termini by 36 amino acids. SERCA3 transcripts were most abundantly expressed in lymphoid tissues, intestine, pancreas, and prostate. The two human SERCA3 proteins encoded by alternatively spliced transcripts were recognized by the monoclonal antibody PL/IM430 and demonstrated Ca2+ uptake and ATPase activity with an apparent Ca2+ affinity 0.5 pCa unit lower than that of other SERCA gene products. The subcellular distribution of SERCA3 protein was indistinguishable from that of SERCA2b, with expression in the nuclear envelope and in the endoplasmic reticulum throughout the cell. Two variant SERCA3 constructs, huS3-I and huS3-II, were isolated that encode proteins with three amino acid differences: Ala-673 (in huS3-I) substituted for Thr (in huS3-II), Ile-817 substituted for Met, and an insertion of Glu-994. huS3-I displayed a 10-fold lower capacity to transport Ca2+ than huS3-II. more...

Electroneutral cation-chloride cotransporters are widely expressed and perform a variety of physiological roles. A novel gene family of five members, encompassing a Na+-Cl- transporter, two Na+-K+-2Cl- transporters and two K+-Cl- cotransporters, encodes these membrane proteins; homologous genes have also been identified in a prokaryote and a number of lower eukaryotes. The cotransporter proteins share a common predicted membrane topology, with twelve putative transmembrane segments flanked by long hydrophilic N- and C-terminal cytoplasmic domains. The molecular identification of these transporters has had a significant impact on the study of their function, regulation and pathophysiology. more...

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications. more...

The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample. more...

The aim of this study was to determine the delay between clinical suspicion and diagnosis of bronchogenic carcinoma, and between diagnosis and performance of therapeutic thoracotomy. The study population included 598 patients undergoing surgery between October 1995 and September 1996 registered in the Bronchogenic Carcinoma Cooperation Group of SEPAR (BCCG-S), and 49 patients from our hospital undergoing surgery during the same period. The mean delay between diagnosis and thoracotomy was 45.15 days (SD 34.7 days) for BCCG-S patients and 53.5 days (SD 22 days) for our hospital patients. In the second group, mean time elapsing between diagnosis suspicion and performance of bronchoscopy was known to be 9.5 days (SD 14.7 days), with the lowest periods recorded for inpatients (3.1 +/- 1.7 days) and for patients who did not require chest x ray guided bronchoscopy (5 +/- 5.8 days). These data are similar to those published for hospitals in other countries. They must be considered long delays and should be shortened. more...

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. more...

The aim of this study was to determine the clinical, radiologic and endoscopic characteristics of adults with tracheobronchial foreign bodies (FB), and to review the role of fiberoptic bronchoscopy in extracting them. We reviewed the case histories and bronchoscopic reports for all patients over 14 years of age with FB treated between 1976 and 1995. Fifty-nine FB were removed from 56 patients; 68% were male and 48% were over 60 years of age. The most common clinical presentations were symptoms of respiratory infection and acute choking. In only in 28% could a risk factor for aspiration be identified. The X-ray was non specific and in 37% of cases the chest film was normal. In 66% FB aspiration was an unexpected endoscopic finding. The FB was removed from the right lung in 81.3%. FB were food items in 71% of cases. Fiberoptic bronchoscopy was useful for removal in 95% of cases, with few and unimportant complications. Two cases were resolved with rigid bronchoscopy and only one patient required surgery. FB aspiration is common and diagnosis is difficult in the adult. Fiberoptic bronchoscopy resolved most aspirations in adults with no important complications. The rigid bronchoscope should be reserved for very specific cases. more...

Background/aims: Due to structural and functional similarities between platelets and vascular smooth muscle cells, platelet cytosolic calcium concentration ([Ca2+]i) has been suggested to be a useful tool to study regulatory mechanisms of peripheral vascular tone. The aim of the present study was to investigate platelet [Ca2+]i in patients with cirrhosis and whether this parameter is related with the systemic and splanchnic vasodilatation found in these patients., Methods: Seventeen patients with cirrhosis and eight age- and sex-matched controls were studied. Mean arterial pressure, cardiac output, femoral blood flow and basal and thrombin-stimulated platelet [Ca2+]i were measured. Cardiac output (thermal dilution), azygos blood flow, hepatic venous pressure gradient and hepatic blood flow were also measured in patients with cirrhosis., Results: Patients with cirrhosis had severe portal hypertension and a significantly higher cardiac output and femoral blood flow and a significantly lower systemic and femoral vascular resistance than controls. Patients with cirrhosis had a lower basal platelet [Ca2+]i than normal subjects. However, there was no relationship between platelet [Ca2+]i and any of the hemodynamic parameters that evaluate systemic or splanchnic vasodilatation., Conclusions: This study shows that cirrhotic patients with portal hypertension have a significant reduction in platelet basal [Ca2+]i. The lack of correlation between platelet [Ca2+]i and hepatic and systemic hemodynamics does not support the use of platelet [Ca2+]i as a model to study mechanisms involved in the pathophysiology of the hyperdynamic circulation associated to portal hypertension. more...

To describe the clinical and radiologic signs, evolution and response to treatment of patients diagnosed of tracheobronchial granular cell tumors (GCT) in our practice. Retrospective computerized review of all bronchoscopic procedures performed in our hospital from January 1974 through November 1996. Patients with GCT were identified and their case histories reviewed. Eight male patients with 9 GCT were identified. Mean age was 55 years. Only one was symptomatic (hemoptysis) and only one had radiologic signs (solitary pulmonary node). Six patients were diagnosed of tumors in other organs. With the exception of one GCT located in the trachea, all were found in the right bronchial system. Endoscopy revealed mucosal abnormalities in six patients and nodes in three. Treatment was conservative in four patients, endoscopic in three (2 mechanical endoscopic resections and one laser Nd-YAG resection in a patient with two tumors), and surgical in one. Disease evolution as treated was favorable during the observation period. Tracheobronchial GCT are rare tumors. Most patients were between 50 and 70 years old, were often asymptomatic and had few radiologic manifestations. They suffered accompanying neoplasia in other organs. GCT were located in central and segmentary bronchial and nodes or abnormal mucosa could be seen endoscopically. Treatment was conservative, endoscopic or surgical, depending on tumor size and patient characteristics. more...

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. more...

A thiazide sensitive Na-Cl cotransporter, rTSC1, has recently been cloned from a rat kidney cortex cDNA library. The molecular regulation and nephron localization of this protein is unknown. The purpose of this study was to examine the nephron distribution and subcellular localization of the rTSC1 protein in the rat kidney. In situ hybridization showed rTSC1 transcripts were localized to short, convoluted tubule segments in the kidney cortex. Polyclonal antibodies raised against a 110 amino acid segment from the amino terminus of rTSC1 recognized three major bands of 135, 140 and 155 kDa on Western blotting of membrane protein from cortex but not outer medulla of the rat kidney. Immunofluorescence studies using the antibody alone and in double labeling experiments with antibodies against the H+ ATPase and calbindin D28, showed intense labeling of apical membranes in the distal nephron beginning in the initial distal convoluted tubule and terminating within the connecting tubule. The intensity of labeling diminished from proximal to distal sites along the distal tubule. Ultrastructural studies by immunoelectron microscopy showed the cotransporter protein to be localized predominately on apical microvilli of the distal convoluted tubule cells. These results are consistent with rTSC1 encoding the apical thiazide sensitive Na-Cl cotransporter in the distal tubule. more...

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. more...

We analysed the effect of ethanol on basal cytosolic-free calcium concentration ([Ca2+]i) in cultured rat myocytes. Ethanol caused a dose-dependent decrease of the resting [Ca2+]i. Removal of ethanol was followed by a transitory increase of [Ca2+]i above the basal level. In cells chronically exposed to ethanol, [Ca2+]i normalized to the previous level. more...

To investigate the possible relationships between blood pressure, parathyroid hormone (PTH) and platelet cytosolic Ca2+ concentration ([Ca2+]i) in patients with essential hypertension, we studied 17 patients with this disease aged 48 +/- 2 years and 17 normotensive controls aged 44 +/- 3 years. Platelet [Ca2+]i was measured by spectrofluorimetry using the dye Fura-2 acetoxymethylester. Patients with essential hypertension displayed lower levels of serum ionized Ca2+ (0.99 +/- 0.03 versus 1.1 +/- 0.01 mmol/l, P < 0.05) and higher serum intact PTH levels (37 +/- 3 versus 26 +/- pg/ml, (P < 0.01) than the normotensive controls. Although serum levels of intact PTH were significantly correlated with mean arterial pressure (MAP) in the combined group of subjects (r = 0.42, P < 0.05), there was no correlation when each group was considered separately. Resting platelet [Ca2+]i was also higher in patients than in controls (57 +/- 3 versus 48 +/- 2 nmol/l, P < 0.005). When platelets were stimulated in vitro with thrombin, the increment in [Ca2+]i was also greater in patients than in controls in the presence of extracellular Ca2+ (264 +/- 24 versus 194 +/- 19 nmol/l, P < 0.05) but not in its absence (123 +/- 12 versus 112 +/- 10 nmol/l). The thrombin-induced increment in [Ca2+]i was correlated with MAP in the hypertensive patients (r = 0.64, P < 0.01) and in the combined group of subjects (r = 0.42, P < 0.05). There was no relationship between resting or thrombin-induced [Ca2+]i and serum PTH in either group of patients or in the combined group of subjects.(ABSTRACT TRUNCATED AT 250 WORDS) more...

The aim was to investigate circulating levels of immunoreactive endothelin (ir-ET) in atherosclerotic renovascular hypertension (RVH), and to assess the role of the kidneys in its overall plasma concentration. We studied 16 hypertensive patients with renal artery stenosis evidenced by angiography and admitted to hospital for the diagnostic evaluation of RVH by renal vein plasma renin activity (PRA) determinations. The right femoral vein was catheterized to simultaneously measure PRA and ir-ET in both renal veins and inferior vena cava below the origin of the renal veins. RVH was present in 9 patients as indicated by diagnostic PRA renal vein ratios and the remaining 7 patients were considered to have essential hypertension (EH). Patients with RVH showed a marked increase in systemic plasma ir-ET concentration (10.3 +/- 0.9 pg/ml). Despite a significant increase of PRA in the vein of the ischemic (IK) versus the contralateral (CK) kidney in patients with RVH, no significant differences in ir-ET concentration were observed between both kidneys. These results indicate that patients with RVH have increased circulating levels of ir-ET. However, the higher systemic plasma ir-ET do not arise from the renal circulation, since plasma ir-ET is significantly higher in systemic circulation than in renal veins. more...

The platelet intracellular calcium concentration ([Ca2+]i) and intracellular pH (pHi) were measured by spectrofluorimetry with the dyes Fura-2 and BCECF, respectively, in 19 patients with essential hypertension (10 males), aged 48 +/- 2 years, before and after 12 weeks of antihypertensive treatment and in 19 normotensive controls (11 males), aged 46 +/- 3 years. [Ca2+]i and pHi were measured in the resting state and after stimulation in vitro with 0.1 U/ml human thrombin. In patients with essential hypertension, both resting [Ca2+]i (61 +/- 4 nmol/l) and thrombin-induced maximal increase in [Ca2]i (291 +/- 26 nmol/l) were significantly (P < 0.01) greater than in the normotensive controls (resting 49 +/- 2 nmol/l and thrombin-induced 199 +/- 21 nmol/l). With respect to pHi, no difference in resting pHi between both groups was found (7.16 +/- 0.01 vs. 7.16 +/- 0.01). However, pHi increment at 300 seconds in response to thrombin was higher in the patients with essential hypertension than in the controls (0.131 +/- 0.02 vs. 0.083 +/- 0.01 pH units, P < 0.05). The increment in pHi was blunted by the amiloride derivative EIPA, indicating that it was mediated by the Na+/H+ exchanger. After antihypertensive therapy in the essential hypertensive patients, basal [Ca2+]i was significantly reduced (52 +/- 2 nmol/l, P < 0.01) and was not statistically different to the value found in the normotensive controls. Resting pHi suffered no significant modification after treatment (7.17 +/- 0.01, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) more...

To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 +/- 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 +/- 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 +/- 3 vs. 48 +/- 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 +/- 0.01 vs. 7.16 +/- 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 +/- 21 vs. 206 +/- 19; P < 0.05) as was the pHi increment (EH: 0.137 +/- 0.01; NT: 0.095 +/- 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) more...

Mitomycin C (MMC) is an alkylating agent that has been recently associated with the hemolytic-uremic syndrome (HUS). Pulmonary impairment in the HUS is rarely reported in the literature, and no reports of pulmonary hemorrhage, as a clinical feature of the HUS, have been documented. We describe two women who developed HUS after MMC therapy and presented massive pulmonary bleeding. Pulmonary hemorrhage is an uncommon feature in the HUS, and seems to appear especially in the HUS associated with MMC therapy. It is extremely resistant to standard treatment, and confers a poor prognosis for this disease. more...

A 43-year-old man with ankylosing spondylitis (AS) was admitted with proteinuria and renal insufficiency. Coincidental IgA nephropathy and secondary renal amyloidosis were diagnosed on renal biopsy. This is the first case reported of coincidental IgA nephropathy and renal amyloidosis as a cause of renal insufficiency in a patient with AS. Both entities should be considered in the diagnosis in a patient with AS and renal impairment. A careful study of the renal tissue including, Congo red stain and immunofluorescence studies is necessary to establish a correct diagnosis in these patients. more...

Cytomegalovirus (CMV) is an ubiquitous agent and is recognized as a pathogen in all age groups. Although symptomatic infection by CMV (CMV disease) in normal adults is generally mild, the virus is known to produce severe symptoms, mostly in immunocompromised patients. In this group of patients, the primary involvement of the colon by CMV is reported to be rare. However, chronic renal failure patients are prone to CMV infection. Nevertheless, despite the high incidence of infection in these patients and the recognition of a defective immune response in some of them, clinical manifestations are an exception. Two chronic renal failure patients who developed acute colitis due to CMV infection are presented. Of interest are the rarity of the association, the favorable clinical course and the differential diagnosis with other gastrointestinal disorders which are more common in these patients. more...

The aim of the present study was to evaluate the regulatory relationship between the cytosolic free calcium concentration ([Ca2+]i and cytosolic pH (pHi). [Ca2+]i and pHi were measured using the fluorescent dyes fura-2 and BCECF [2',7'-bis-(carboxyethyl)-5,6-carboxyfluorescein] respectively. In a medium with 1 mmol/l extracellular calcium, thrombin (2.5 units/ml) induced an increment in [Ca2+]i of 638 +/- 31 nmol/l (n = 5) and an intracellular alkalinization of 0.14 +/- 0.01 pH units (n = 8). Both responses were dependent on the concentration of thrombin, displaying a sigmoidal dose-response pattern. The intracellular alkalinization was dependent upon extracellular Na+ and was amiloride-sensitive, indicating that it was mediated by activation of the Na+/H+ exchanger. When extracellular calcium was chelated with EGTA prior to the addition of thrombin, the intracellular alkalinization was not affected (0.15 +/- 0.02 at 2.5 units/ml thrombin, n = 8). Under these circumstances, the [Ca2+]i increment represents mobilization from internal stores, reaching 157 +/- 42 nmol/l at 2.5 units/ml thrombin. When platelets were preloaded with the intracellular calcium chelator MAPTAM (1,2-bis-5-methylaminophenoxylethane-NNN'-tetraacetoxymethyl acetate) to block the increase in [Ca2+]i induced by thrombin, no increment in pHi was observed. Moreover, MAPTAM-loaded calcium-depleted platelets had a basal pHi that was more acidic than in the presence of 1 mmol/l extracellular calcium (6.93 +/- 0.09 versus 7.14 +/- 0.01, n = 26, P < 0.001). Ionomycin induced an elevation of [Ca2+]i that was accompanied by a concomitant increase in pHi, which was Na(+)-dependent and amiloride-sensitive. [Ca2+]i and pHi increases induced by ionomycin were both dependent on the concentration of ionomycin. In conclusion, an increase in [Ca2+]i is necessary for the agonist-induced activation of the Na+/H+ exchanger in platelets. Non-agonist-induced increases in [Ca2+]i seems to prompt activation of the exchanger. In addition, Ca(2+)-depleted platelets have a more acidic basal pHi, indicating that the basal level of [Ca2+]i is also important for maintaining the basal pHi. more...

Chronic renal failure patients are prone to soft tissue calcifications. A phenomenon of acute ischemic skin necrosis and dermohypodermic arteriolar medial calcification has been described recently in patients with chronic renal failure and secondary hyperparathyroidism (HPT). This phenomenon, termed calciphylaxis, occurs in response to certain factors, the most important of which appears to be an elevated blood calcium-phosphate product. Accordingly, parathyroidectomy in addition to normalization of calcium-phosphate product has been proposed as the only effective therapeutic approach for this condition. We describe a case of chronic renal failure with severe secondary HPT in which the patient developed calciphylaxis 4 days after the appearance of a psoriatic flare. Four months before, a subtotal parathyroidectomy was performed for severe HPT and at the time the ulcerations appeared, blood calcium-phosphate product was correct. Etiological and physiopathological aspects of calciphylaxis are discussed. more...

Pheochromocytoma is a catecholamine secreting tumor which has been traditionally considered as a potentially curable cause of hypertension. However, the existence of malignant pheochromocytomas as well as the problem which the recurrence of benign pheochromocytomas present, make the eradication of this tumor more complicated. It is note worthy the difficulty in localizing recurrent pheochromocytomas as well as the prognostic interest that presents the possibility of differentiating between recurrence and metastasis. We refer the case of a female patient suffering benign adrenal pheochromocytoma, who, 10 years it was surgically removed, presented a relapse of symptoms, and was diagnosed of extra-adrenal pheochromocytoma, in Zuckerkandl organ. The importance of performing a long term post-surgical follow-up in these patients is stressed. more...

A case of prosthetic valve endocarditis caused by Corynebacterium pilosum in a 79-year-old woman developed eighty years after aortic valve replacement with bovine pericardium bioprosthesis is described. In spite of the antibiotic therapy she presented an unfavourable course that led to her death. more...

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. more...

To assess the effect of chronic exposure to high circulating catecholamine concentrations on the beta 2-adrenergic receptors, the density and affinity of lymphocyte beta 2-adrenergic receptors were measured in 5 patients with pheochromocytoma (2 males and 3 females, with a mean age of 39 +/- 12 years). In 4 patients the studies were repeated 15 days after tumor removal. Before surgery, all patients had high plasma catecholamine concentration. The density of beta 2-adrenergic receptors was reduced, although their affinity was within the reference range. There was an inverse correlation between plasma epinephrine concentration and beta 2-adrenergic receptor density (r = -0.959, p = 0.01). After surgical resection, plasma catecholamine concentrations and receptor density became normal. The dissociation constant decreased in the four patients. In conclusion, in the presence of chronically high levels of circulating catecholamines the density of lymphocyte beta 2-adrenergic receptors is reduced. However, it becomes normal when plasma catecholamine concentration returns to the reference values, the dynamic character of this regulation being thus shown. The measurement of these receptors in the lymphocyte could be useful for the diagnosis and follow up of patients with pheochromocytoma. more...

Mitomycin C (MMC) is an alkylating agent which has been associated with microangiopathic hemolytic anemia and acute renal failure, with an overall incidence between 2 and 10%. This complication can develop several months after the initiation of chemotherapy. Isolated renal impairment without overt microangiopathic hemolytic anemia, although reported, is less frequently documented. We describe a 63-year-old man who developed progressive renal failure without any evidence of hemolysis or thrombopenia 10 months after beginning chemotherapy with MMC and Ftorafur. A renal biopsy displayed features of microangiopathy. The patient required the institution of chronic hemodialysis. In conclusion, it is important to be aware of this indolent but severe renal complication in patients treated with MMC. Urinary parameters and renal function should be monitored over a long period for an early diagnosis. more...

The vascular involvement of Behçet's disease is nowadays considered as an important sign of the clinical evolution of these patients. It can affect both the arterial and the venous territories. Superficial thrombophlebitis is the most common vascular manifestation. Thrombosis of deep veins is relatively rare and it generally appears within the inferior vena cava territory as a late manifestation in the evolution of the disease. We describe two cases of Behçet's disease which presented, at an early stage, thrombosis of the superior vena cava as the more relevant manifestation of the disease. The evolution of both patients was satisfactory with the combination of cyclophosphamide and colchicine. The etiopathogenesis of this manifestation and its therapeutic possibilities are discussed. more...