More about anaphylactoid reactions in patients dialyzed with AN69 filter and on angiotensin converting enzyme inhibitors treatment.
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Biomedical subjects
Publications and source records attributed to M C García.
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Intravenous immunoglobulin (IV Ig) has been shown its therapeutic value in primary immunodeficiency diseases associated with a profound impairement of IgG-mediated antibody production. In recent years its range of indications has been extended to some secondary immunodeficiency disorders such as chronic lymphocytic leukemia and children with symptomatic HIV infection IV Ig is also of value in cytomegalovirus infection in transplant recipients. The use of IV Ig in some immunoregulatory disorders, namely immune thrombocytopenic purpura and Kawasaki syndrome has also been proved. Preliminary studies suggests a benefit in myasthenia gravis, Guillain-Barré syndrome, polymyositis, chronic demyelinating diseases and steroid dependent asthma. Little is known about the mechanism of action of IV Ig in these immunoregulatory disorders. In sum, IV Ig has a few proved indications and many potential ones. Carefully controlled clinical trials are needed to determine the effectiveness of IV Ig in these conditions.
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Synthesis of enterotoxins C1 and C2 and thermonuclease throughout the growth cycle was investigated with Staphylococcus aureus type strains FRI137 and FRI361 and S. aureus isolates M5 (C1) and L2 (C2) of animal origin. Both enterotoxins were produced during the exponential growth phase or at the beginning of the stationary phase. The minimal incubation time (7 to 12 h) and the lowest population (10(7) to 2 x 10(9) CFU/ml) associated with detectable enterotoxin (1 to 6.5 ng/ml) were related to the total amount of toxin produced after 24 h. Thermonuclease was detected in all samples whenever enterotoxins were detected. Furthermore, strain FRI137 produced thermonuclease earlier and at lower cell populations than it did enterotoxin C1. Patterns of enterotoxin and thermonuclease synthesis did not correlate. The concentration of toxins increased throughout the growth cycle, while the concentration of thermonuclease remained constant during the last hours of the growth cycle.
PCA 4233 [2-(phenylthio)ethyl-5-ethoxycarbonyl-2,4,6-trimethyl- 1,4-dihydropyridine-3-carboxylate] and PCA 4248 [2-(phenylthio) ethyl-5-methoxycarbonyl-2, 4, 6-trimethyl-1, 4-dihydropyridine-3-carboxylate], two compounds developed from a series of 1,4-dihydropyridines that lack pharmacologic effects on voltage-operated calcium channels, were found to block selectively rabbit operated calcium channels, were found to block selectively rabbit and human platelet aggregation and secretion, and binding of [3H]-labeled platelet-activating factor (PAF) to human platelet and polymorphonuclear PAF receptors. Rabbit platelet aggregation was tested with 1.9 nM PAF, i.e., a concentration producing maximal response, and was completely blocked with 10 microM PCA 4233 and 3 microM 4248 (IC50 values, 2.55 and 1.05 microM, respectively). Human platelet aggregation in platelet-rich plasma was studied with 1 microM PAF, a concentration that caused a response comparable with that of 1.9 nM PAF in rabbit platelets. The IC50 of PCA 4248 for ATP release under these conditions was 3.6 microM. PCA 4248 behaved as a competitive and selective antagonist in [3H]serotonin secretion studies on rabbit platelets, since it displaced rightwards log dose-response curves and lacked any effect on thrombin- and ionophore A23187-induced platelet secretion. A pA2 value of 7.5 was obtained from Schild plots on [3H]serotonin secretion studies. PCA 4248 also produced a dose-dependent inhibition of [3H]PAF binding to human platelets and to human polymorphonuclear leukocytes. These data indicate that PCA 4233 and PCA 4248 belong to a new class of selective PAF-receptor antagonists.
In 12 members of a family with MODY, insulin and C-peptide release after intake of a test breakfast was measured as well as binding of insulin to its erythrocyte receptor. According to serum glucose concentrations, subjects were classified into: diabetic, carbohydrate intolerant, and normal subjects. The two diabetic patients had an insulin release pattern similar to that of non-insulin dependent diabetics. The two patients with carbohydrate intolerance presented hyperinsulinism either at base state and after stimulation. Of the eight normal subjects, three presented high concentrations of serum insulin either at base level and after stimulation; in the remaining five, base insulinemia was normal and the response after food intake was poor. Insulin binding to the receptor was decreased in diabetic patients and this anomaly was more evident in patients with carbohydrate intolerance. In the three patients with increased serum insulin concentration, no disturbances in insulin-receptor binding were detected; in the remaining five patients, insulin-receptor binding was significantly decreased. Our findings prove that these subjects present a disturbance of insulin release and an impairment of insulin-receptor binding with a predominance of one or the other alteration even before hyperglycemia is evident.
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Staphylococcus aureus strains FRI 137 (enterotoxin C1 producer) and FRI 361 and L 2 (enterotoxin C2 producers) were grown alone and in the presence of a mixed commercial starter culture (Streptococcus lactis, Streptococcus cremoris and Streptococcus lactis subsp. diacetylactis). Lactic acid bacteria had a slight inhibitory effect on S. aureus population and only during the late stages of growth. In contrast, enterotoxin synthesis was strongly inhibited, inhibition at 18 h being 89% (FRI 137), 80% (FRI 361) and 69% (L 2). Enterotoxin C1 was produced and accumulated during all phases of growth in pure and mixed culture, but associative growth resulted in reduction of enterotoxin C2 after 24-36 h. In mixed culture, high producers of thermonuclease (FRI 137 and L 2) showed an early decrease in enzyme activity followed by an increase, but it never reached levels attained in pure culture. Thermonuclease was detected whenever enterotoxin was detected, but production curves did not parallel each other.
Burgos cheese was manufactured from pasteurized ewes' milk inoculated with Staphylococcus aureus strains FRI 137 and FRI 361, at levels of ca 10(3) and 10(5) cfu/ml and stored at 4 degrees, 10 degrees and 15 degrees C and at room temperature (10 degrees-15 degrees C). Populations of Staph. aureus and mesophilic aerobes, pH, and production of thermonuclease and enterotoxins C1 and C2 were investigated. Aerobic counts increased during cheese-making and storage. With both test strains, important growth was observed only during the storage period, the larger levels corresponding to the higher temperatures. Although Staph. aureus strains attained populations of over 10(8) cfu/g, no enterotoxin was detected. Strain FRI 361 reached 10(7) cfu/g without production of a detectable amount of thermonuclease. With strain FRI 137, the minimal population associated with enzyme activity was influenced by the inoculum size. Staphylococcus aureus counts are better indicators of staphylococcal growth in Burgos cheese than the thermonuclease test.
1. Modulation of fast and slow Ca2+ channels of frog skeletal muscle by adrenaline (10(-6) to 10(-5) M) and cyclic AMP was investigated using intracellular voltage recordings in intact fibres and a voltage-clamp technique in cut fibres. 2. In tetraethylammonium (TEA), Cl(-)-free Ringer solution, adrenaline increased the maximum rate of rise of Ca2+ spikes by 85% and in a similar solution, peak slow Ca2+ current (ICa,s) by 51%. 3. Application of cyclic AMP to the cut ends of fibres, produced a relative increase of ICa,s of ca. 24%. The effect was maintained for ca. 2 h. 4. Changes in the time course of ICa,s were produced by adrenaline and cyclic AMP: the limiting values of time-to-peak current measured as a function of membrane potential were lower (ca. 41% in adrenaline and ca. 34% in cyclic AMP) than those found in control experiments. Also, ICa,s decayed faster in the presence of adrenaline or cyclic AMP. These changes can be explained by exhaustion of Ca2+ in the lumen of transverse tubular system and do not require the assumption of kinetic variations. 5. Fast Ca2+ currents (ICa,f) which could not be blocked by nifedipine were also recorded. Cyclic AMP greatly increased the amplitude of ICa,f but had no obvious effects on ICa,f kinetics. 6. Application of catalytic subunit of cyclic AMP-dependent protein kinase by diffusion or by pressure injection also increased the amplitude of ICa,s and ICa,f. Pressure injection brought about modifications in the time course of ICa,s that cannot be explained by depletion of Ca2+. 7. Mechanical experiments were performed on single fibres. Nominally Ca2+-free solutions prevented the development and the maintenance of positive inotropic effect of adrenaline on twitch tension. Development of twitch potentiation was dependent upon the frequency of stimulation. Adrenaline was practically ineffective if no stimulation was applied. 8. It is concluded that both populations of Ca2+ channels are modulated by adrenergic stimulation probably via cyclic AMP, and that twitch potentiation may be mediated by a Ca2+ entry through Ca2+ channels.
Principal component analysis was used to examine the correlations between two sets of variables, one representing physicochemical characteristics (pH, aw and NaCl, moisture and fat content) of Manchego (36 samples) and Burgos (36 samples) cheeses, and the other representing counts of several microbial groups (mesophiles, psychrotrophs, lactic acid bacteria, coliforms, enterococci, staphylococci and molds and yeasts). Thermonuclease content was also included. In addition to the expected relationships (NaCl content, moisture, aw, etc.), significant correlations between some compositional characteristics and levels of certain microorganisms were found. These correlations were dependent on the type of cheese. Thermonuclease content was positively related to enterococci and ripening (only in Manchego cheese). In contrast to former observations, no relationships were observed between coliforms and enterococci counts.
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Intravenous transfusion of blood plasma or serum from electroacupuncturally stimulated donor rabbits that displayed unilateral analgesia of a specific region of one hindlimb as shown by the lack of flexor withdrawal responses to pin pricks, caused the development of a comparable region of analgesia in naive, recipient rabbits. The site of this analgesia was comparable to that observed in the donor animals in terms of anatomical region and in terms of laterality. These findings indicate that acupunctural analgesia is induced through highly specific nervous and chemical mechanisms and that the substances produced can distinguish specific body regions located on one side of the body from the other.
Small doses of iodide (2 times 3.2 mug at 12 h interval), below those capable of inducing Wolff-Chaikoff effect, were injected into rats kept on a moderately low iodine diet. By means of a 125I equilibration technique as well as by direct measurement of cold T4, it was demonstrated that the level of circulating PB125I (representing iodothyronines as confirmed by column chromatography) increased by a mean of 40% within 24 h following the first iodide injection. The serum TSH concentration (measured by radioimmunoassay) was simultaneously depressed. Thus, in stimulated thyroid glands, a biologically significant fraction of an iodide load escapes autoregulatory control of iodothyronine synthesis. A small, transient increase of hormone release is likely to represent the physiological response of a normal gland to a sudden supplement of iodide supply. The ensuing depression of TSH secretion may be necessary for final adjustment of thyroid function. It is considered to be the last step in a cascade of mechanisms whose interaction keeps the thyroidal hormone output within narrow limits in the face of a fluctuating iodide supply. Failure of one or several of these mechanisms in the goitrous human gland could conceivable explain the phenomenon of "Jod Basedow".
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The mortality among end-stage renal failure (ESRF) patients undergoing renal replacement therapy (RRT) remains high. An important proportion of these patients die shortly after the initiation of RRT. The present study aims to determine the best predictors for the early mortality in a group of 140 ESRF patients who initiated RRT between october 96 and december 99. The mean age of the study group was 61 +/- 13 years, and the mean follow-up time was 20 +/- 12 months. Diabetic nephropathy was the most prevalent etiology of renal failure (30%). The following data, collected immediately before the initiation of RRT, were included as independent variables: demographic and clinical characteristics, including the nutritional status established by the Subjective Global Assessment (SGA), follow-up time in the predialysis clinic (less or longer than 3 months), EPO therapy, vascular access, renal function (creatinine and urea clearances, and Kt/V urea), hematological and biochemical data including serum albumin, bicarbonate, transferrin, PTH and C-Reactive protein, as well as the protein catabolic rate and the percent of lean body mass normalized for ideal body weight, calculated from the 24 h total urine excretion of nitrogen and creatinine. The Cox proportional hazard regression model, stratified for an age over or less than 65 year, was utilized to determine the best predictors for the mortality during the study period. Sixty percent of patients had at least one comorbid condition, and 35% had cardiovascular diseases. Mild-moderate or severe malnutrition was observed in 48% of patients. The creatinine clearance and Kt/V urea before the initiation of RRT were: 9.50 +/- 2.64 ml/min/1.73 m2 and 1.47 +/- 0.44, respectively. Forty-one patients died during the study period (annual death rate: 17%). The best predictor of mortality was the nutritional status assessed by the SGA (OR: 2.32, IC 95% 1.54-3.48, p < 0.0001). In a second analysis in which the SGA was removed from the model, the previous history of cardiovascular diseases (OR: 2.07, CI 95%: 1.06-4.06, p = 0.032), and the percent of lean body mass/ideal weight (OR: 0.96; IC 95%: 0.93-0.99; p = 0.042), proved to be the best predictor of mortality. In conclusion, nutritional indices prior to the initiation of RRT, and the previous history of cardiovascular diseases were the best predictors of the early mortality in this unselected population on dialysis. Because nutritional status appeared to be a marker of the severity of the comorbid conditions, a better control of the number and severity of these comorbid conditions may be the best way for reducing the mortality in patients on RRT.