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Biomedical subjects

M Pascual

Publications and source records attributed to M Pascual.

At least 145 records · Page 8Linked to original sources
PubMed1991

Stroke secondary to multiple spontaneous cholesterol emboli.

We describe one male, 49-year-old diabetic patient in whom regressive stroke with aphasia and right-sided hemiparesia was related to multiple small emboli in the left paraventricular cortex. Simultaneous presence of several cholesterol emboli in the left eye ground and detection of an atheromatous plaque at the homolateral carotid bifurcation let assume that the cerebral emboli originated from that plaque and also consisted of cholesterol crystals. The patient was discharged on low-dose aspirin (100 mg/day) after neurologic improvement. Follow-up at one year revealed clinical stability, recurrence of the cholesterol emboli at the eye ground examination and no change of the carotid plaque. Cholesterol embolization with renal failure, hypertension and peripheral arterial occlusions causing skin ulcerations is classical in case of atheromatous aortic disease but stroke has rarely been reported in this syndrome. However, more frequent use of invasive procedures (arteriography, transluminal angioplasty, vascular surgery) or thrombolytic treatment might increase its incidence in the near future.

Carotid Artery Thrombosis↗
PubMed1990

[Neurogenic pulmonary edema complicating a generalized epileptic crisis].

Epileptic seizures may be rapidly followed by neurologic pulmonary edema (NPE). While the outcome of respiratory failure may be spontaneously favourable, in some cases death may occur due to respiratory and/or neurologic dysfunction. Two patients with NPE are described, one of whom survived without treatment and is in good health. In the other the outcome was rapidly fatal despite prompt and vigorous medical treatment.

Adult↗
PubMed1990

A monoclonal antibody which blocks the function of factor D of human complement.

Factor D is an essential enzyme for activation of complement by the alternative pathway (AP). It has been difficult to obtain mouse monoclonal antibodies (Mabs) which block the function of factor D. We have developed a strategy to obtain such Mabs using a double screening procedure of the initial clones. We selected the clone whose supernatant had the lowest level of anti-factor D Ab by ELISA and abolished factor D haemolytic activity. Addition of this Mab to human serum was shown to abolish conversion of C3 by cobra venom factor, haemolysis of rabbit erythrocytes, and activation of C3 and C5 by cuprophane dialysis membranes.

Animals↗
PubMed1989

Complement activation by the alternative pathway is modified in renal failure: the role of factor D.

Factor D, an essential enzyme of the alternative pathway (AP) of complement, is eliminated by the kidney, and its plasma concentration increases 10-fold in end-stage renal disease (ESRD). The purpose of this study was to analyze the consequences of factor D accumulation. A number of in vitro assays were used to analyze AP activation in normal human serum (NHS), in normal serum supplemented with purified factor D to 10-fold its normal concentration (10 x D), and in sera of patients with ESRD. When compared with NHS, in 10 x D: 1) Spontaneous fluid-phase activation of complement at 37 degrees C was greatly increased as measured by C3 cleavage, 2) The lysis of rabbit erythrocytes, a function of the AP, was accelerated, 3) More C3 fragments bound to cuprophane membranes and to immune precipitates; both reactions were accompanied by the formation of more C5a, 4) Complement mediated solubilization of antigen-antibody precipitates was enhanced. Sera of patients with ESRD behaved similarly to 10 x D in all assays used, i.e., enhanced AP function, although complement activation measured in these assays varied widely from one individual to another. Thus, the elevated factor D concentration observed in renal failure might have important pathophysiological consequences, some of which could be detrimental (e.g., C5a produced during hemodialysis), while others might be beneficial, e.g., solubilization of immune precipitates.

Aged↗
PubMed1988

Solubilization of immune precipitates by complement in the absence of properdin or factor D.

Various experiments have demonstrated that immune precipitates (IPs) are not solubilized by complement in the absence of alternative pathway function. To determine whether the characteristics of the IPs were responsible for these observations, we studied the solubilization (Sol) of IPs formed by bovine serum albumin (BSA)-rabbit antiBSA and tetanus toxoid (TT)-human antiTT. Sera deficient in properdin solubilized a fraction of BSA-antiBSA precipitates, although only when the IPs were formed in antibody excess. The same sera solubilized TT-antiTT precipitates with some delay but almost as efficiently as normal serum. Factor D-depleted serum solubilized a fraction of TT-antiTT precipitates too, indicating that Sol may proceed through activation of the classical pathway only. Thus, the requirements for complement-mediated Sol depend on the characteristics of the IPs and do not necessarily include alternative pathway function.

Antibodies↗
PubMed1988

Metabolism of complement factor D in renal failure.

Factor D is an essential enzyme of the alternative pathway of complement. Its plasma concentration increases approximately tenfold in end-stage renal failure (ESRF). To analyze its metabolism in humans, we injected purified radiolabelled factor D into 5 healthy individuals and 12 patients with various renal diseases or renal failure. Fractional metabolic rates (FMR) and extravascular/intravascular distributions (EV/IV) were calculated using a compartmental model. The FMR was very rapid in normal individuals (mean 59.6%/hr; range 74.1 to 50.5), significantly diminished in the five patients with ESRF (5.7%/hr; 7.0 to 2.8; P less than 0.004), and correlated well with the creatinine clearance (r = 0.89; P less than 0.001). The extrarenal catabolic rate was not modified in renal failure. Despite a significant inverse correlation between plasma levels of factor D and creatinine clearance [r = 0.68; P less than 0.002], factor D levels were not a sensitive indicator of renal function because the synthesis rate (SR) varied widely from one individual to another (mean SR: 62.9 micrograms/kg/hr; 14.9 to 136.5). Factor D synthesis was not significantly altered by renal function, and did not correlate with C-reactive protein, suggesting that factor D is not an acute phase protein. The proportion of intact factor D elimination in the urine was increased in patients with tubular dysfunction (up to 15% compared to less than 0.2% in normal individuals) confirming that under normal circumstances factor D is filtered through the glomerulus and catabolized by tubular cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement Activating Enzymes↗
PubMed1987

Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia.

Repeated episodes of febrile panniculitis and hepatitis were the main clinical features in two patients with an IgG1 kappa paraproteinemia and severe depletion of the early components of the classical pathway of complement (acquired C1 inhibitor deficiency). They did not have episodes of cutaneous angioedema or evidence of immune complex disease. In the more severely affected patient, the episodes responded to steroids. These features have not been described with acquired C1 inhibitor deficiency and may be related to complement activation.

Complement Activation↗
PubMed1987

Fast liver catabolism of C1q in patients with paraproteinaemia and depletion of the classical pathway of complement.

The main clinical features in four patients with IgG1k paraproteinaemia and acquired complement deficiency included xanthomatous skin lesions (in three), panniculitis (in three) and hepatitis (in two). Hypocomplementaemia concerned the early classical pathway components--in particular C1q. Metabolic studies employing 125I-C1q revealed a much faster catabolism of this protein in the four patients than in five normal controls and three patients with cryoglobulinaemia (mean fractional catabolic rates respectively: 23.35%/h; 1.44%/h; 5.84%/h). Various experiments were designed to characterize the mechanism of the hypocomplementaemia: the patients' serum, purified paraprotein, blood cells, bone marrow cells, or xanthomatous skin lesions did not produce significant complement activation or C1q binding. When three of the patients (two with panniculitis and hepatitis) were injected with 123I-C1q, sequential gamma-camera imaging demonstrated rapid accumulation of the radionuclide in the liver, suggesting that complement activation takes place in the liver where it could produce damage.

Adult↗
PubMed1984

Epidermal growth factor receptors in human breast cancer.

The capacity for specific binding of 125I-epidermal growth factor (EGF) was studied in crude membrane fractions from 95 human breast carcinomas. About 42% of the samples showed saturable, high affinity, specific binding of EGF. In 21% of the tumors we were able to demonstrate high (above 10 fmoles/mg protein) binding capacity. Moreover, high EGF receptor values were associated with a low content of estradiol receptor. These studies are related to the definition of new biochemical markers in human breast cancer.

Animals↗
PubMedDate not supplied

The binding of immune complexes by the erythrocyte complement receptor 1 (CR1).

Immune complexes, which have reacted with complement and bear C3b fragments, bind to the complement receptor 1 (CR1) on human erythrocytes. Indeed, CR1 on erythrocyte serves as a transport system for immune complexes in the circulation so as to prevent immune complex deposition outside the fixed macrophage system. A defect in this transport system has been described in several diseases, in which either complement levels or CR1 number on erythrocytes are diminished. Recent studies have shown that the binding of immune complexes to erythrocytes is favored by the multiple C3b binding sites per receptor and the clustered distribution of CR1 on the erythrocyte surface. Only a few immune complexes bind per erythrocyte but these complexes are tightly bound. The other main function of CR1 on erythrocytes is to enhance the inactivation of C3b by factor I present in plasma. This reaction allows the release of immune complexes from the erythrocyte surface and their transfer to fixed macrophages.

Animals↗
PubMedDate not supplied

Rapid activation of the alternative pathway of complement by extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is an effective therapy for patients with severe respiratory distress syndromes. However, an inflammatory response has been observed with the use of this therapy. We measured complement activation in vivo in two adults receiving ECMO for acute respiratory distress syndrome (ARDS). Production of complement activation fragments C4d, Bb, iC3b, and SC5b-9 was determined using commercial ELISA kits. In both patients there was intense activation of complement that peaked 1 hour (mean SC5b-9 increase to 1135% of baseline) after the start of ECMO and occurred predominantly via the alternative pathway (Bb production). Early and acute complement activation may be responsible for the initiation of the inflammatory response that has been observed in patients treated with ECMO.

Adult↗
PubMedDate not supplied

[Intestinal occlusion due to pancreatitis mimicking stenosing neoplasm of the splenic angle of the colon].

Colonic involvement in patients with severe acute pancreatitis or chronic pancreatitis is common and complications such as paralytic ileus, segmental necrosis and pancreatic-colonic fistulae have been described. However, mechanical occlusion of the colon due to pancreatitis is infrequent. We present the case of a 45-year-old man with occlusion of the colon secondary to asymptomatic pancreatitis mimicking a locally advanced stenosing neoplasm of the splenic angle. Ten years prior to the present episode the patient had presented acute alcoholic pancreatitis complicated by a pseudocyst requiring surgery. The current reason for admission was abdominal colic pain and constipation with onset 5 days previously. Contrast enema was administered showing colonic occlusion caused by stenosis at the splenic flexure, suggesting the presence of a neoplasm. Urgent laparotomy showed the presence of a tumor originating in the colon that infiltrated the splenic hilum. Subtotal colectomy and en-bloc splenectomy were performed. Histopathological analysis showed pericolonic inflammation and fibrosis secondary to pancreatitis; the colonic mucosa showed no tumoral infiltration. To date, fewer than 30 cases of this infrequent complication have been published.

Acute Disease↗
PubMedDate not supplied

[Quality standards in rectal cancer surgery].

The results of surgery for rectal cancer have classically been measured through indicators such as morbidity, mortality, and length of hospital stay. In the last few years other parameters have been included that evaluate healthcare quality such as the functional results of the surgical technique employed and quality of life. Total resection of the mesorectum, performed by experienced surgeons, is the surgical technique of choice. Currently, the sphincter can be preserved in 70% of patients. Anastomotic dehiscence after anterior resection of the rectum is the most serious complication and the most important risk factor is the height of the anastomosis. The overall dehiscence rate should be less than 15% and operative mortality should be between 2% and 3%. The colonic reservoir improves functional outcome and consequently it is the procedure of choice to reconstruct transit after low anterior resection. Local recurrence should be less than 10% and 5-year survival should be between 70% and 80%. In general, quality of life is better after anterior resection of the rectum than after abdominoperineal amputation, despite the functional deterioration presented by some patients.

Amputation, Surgical↗