Recovery of allograft function after complete withdrawal of immunosuppression.

We describe an interesting case of a patient who recovered function of a previously failed kidney allograft after immunosuppressive medications were discontinued for 4 months, requiring maintenance hemodialysis. He had a split-thickness skin graft to his abdomen because of previous surgical complications. His postoperative course was complicated by sepsis and refractory hypotension. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone. At the same time, hemodialysis was stopped for possible catheter-related infection. The patient recovered function of the previously failed allograft and has not required hemodialysis.

Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls.

The effects of Ca2+ and Ca2+/calmodulin on the polychlorinated biphenyl (PCB)-induced activation of phospholipase A2 (PLA2) in rat neutrophils were examined. The commercial PCB mixture Aroclor 1242 induced activation of PLA2 and promoted an increase in the intracellular free calcium concentration ([Ca2+]i). Bromoenol lactone (BEL), an inhibitor of the Ca2+-independent PLA2 isoform (iPLA2) activated by PCBs, did not abrogate the increase in [Ca2+]i, suggesting that this change in Ca2+ concentration is not downstream from the activation of iPLA2. TMB-8 [8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate], a blocker of the release of intracellular Ca2+, decreased Aroclor 1242-induced stimulation of PLA2 with a maximal inhibition of 17% at 50 microM. These two results suggest little direct dependence between the PCB-induced activation of iPLA2 and increase in [Ca2+]i. Calmidazolium and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], two chemically distinct calmodulin inhibitors, inhibited Aroclor 1242-induced PLA2 activity, whereas trifluoperazine (TFP), another inhibitor of calmodulin, had no effect at noncytotoxic concentrations. Thus, activation of PLA2 is dependent, in part, on calmodulin. Furthermore, both TFP and Aroclor 1242 inhibited neutrophil degranulation stimulated by the bacterial peptide formyl-methionyl-leucyl-phenylalanine. These results raise the possibility that some of the effects of PCBs on neutrophil function can be explained by effects on Ca2+/calmodulin-dependent processes.

Análisis automático de los movimientos alternativos de miembros superiores en pacientes con ataxia espinocerebelosa tipo 2 / Automatic analysis of the alternate movements of the arms in patients with type 2 spino cellular ataxia

Introducción: el paciente con ataxia espinocerebelosa tipo 2 presenta dificultades en la ejecución de los movimientos alternativos tales como la pronación y la supinación. Objetivos: evaluar el desempeño del sistema automatizado para la cuantificación de los trastornos de los movimientos alternativos. Pacientes y métodos: estudiamos la cuantificación de la diadococinesia en dos grupos de sujetos sanos, un primer grupo (64 sujetos) para la determinación de los intervalos de normalidad y el segundo para la validación de la prueba (52 sujetos). Además, fueron incluidos 100 enfermos para realizar la validación del sistema. Otros 53 pacientes se evaluaron antes y después de la rehabilitación. Resultados: el análisis de las medidas básicas para la discriminación diagnóstica de la diadococinesia demostró que la sensibilidad del test era mayor mientras mayor era el punto de corte, y que al analizar la especificidad ocurría un efecto contrario. Así, respecto al punto de corte mayor, la probabilidad de un resultado positivo es aproximadamente cinco veces superior en los enfermos que en los no enfermos, pero la probabilidad de un resultado negativo es seis veces mayor en los no enfermos que en los enfermos. Los resultados del análisis de varianza realizado a pacientes antes y después de la rehabilitación sugirió la existencia de cambios cuantitativos en el segundo estudio como traducción del efecto positivo de la neurorrehabilitación. Conclusión: la técnica empleada es eficaz en la diferenciación de los sujetos enfermos de los sanos y justifica el empleo de las mismas en la evaluación de las capacidades coordinativas tras la rehabilitación(AU)

Introduction: a patient with type 2 spino cerebellar ataxia has difficulty in carrying out alternate movements such as pronation and supination. Objectives: to evaluate the function of an automatized system for measuring disorders of alternate movements. Patients and methods: We studied the measurement of diadochokinesia in two groups of healthy patients, a first group (64 persons) to determine the normal intervals and a second group to validate the test (52 persons). We also studied 100 patients for validation of the system. A further 53 patients were evaluated before and after rehabilitation. Results: analysis of the basic measurements for diagnosis of duodochokinesia showed that the higher the cut off point, the greater the sensitivity of the test, whereas the opposite occurred with the specificity. Thus, regarding a higher cut off, there is a five times greater probability of a positive results in the patients than in healthy persons. However, the probability of a normal result is six times higher in healthy than in affected persons. The results of variant analysis done on patients before and after rehabilitation suggest that the presence of quantitative changes in the second study was due to the positive effect of neuro rehabilitation. Conclusion: the technique used is effective for differentiation of affected from healthy persons and its use is justified in the evaluation of co ordination ability after rehabilitation(AU)

Role of protein phosphorylation in activation of phospholipase A2 by the polychlorinated biphenyl mixture Aroclor 1242.

Polychlorinated biphenyls (PCBs) activate neutrophils to induce degranulation and undergo superoxide production through a mechanism that involves stimulation of phospholipase A(2) (PLA(2)). Since the biochemical processes leading to the PCB-induced activation of this enzyme are unknown, the objective of this study was to determine whether protein phosphorylation has a role in this mechanism. Isolated rat neutrophils were labeled with [(3)H]-arachidonic acid ([(3)H]-AA), and activation of PLA(2) was determined from release of radioactivity into the medium. Exposure to the PCB mixture Aroclor 1242 induced release of [(3)H]-AA, and pretreatment with bromoenol lactone (BEL), an inhibitor of calcium-independent PLA(2), diminished release by 80%. Genistein, an inhibitor of tyrosine kinases, caused a small but significant decrease in Aroclor 1242-stimulated release of [(3)H]-AA. Daidzein, a genistein analog with no activity to inhibit tyrosine kinases, had no effect on [(3)H]-AA release. An inhibitor of p38 mitogen-activated protein kinase (MAPK), SB203580, did not affect Aroclor 1242-induced PLA(2) activity at concentrations selective for p38 MAPK; however, PD 98059, which inhibits MAPK kinase (MEK), decreased [(3)H]-AA release to about the same extent as genistein. Treatment of neutrophils with Aroclor 1242 induced phosphorylation of p44 MAPK, and this phosphorylation was unaffected by BEL but was inhibited by PD 98059. Staurosporine, a nonselective inhibitor of protein kinase C (PKC), inhibited PCB-induced release of [(3)H]-AA. Ro 32-0432, a selective inhibitor of PKC(alpha) and PKC(beta1), produced the greatest degree of inhibition (40%) among the tested protein kinase inhibitors. These results suggest that tyrosine kinases, PKC, and the MEK/MAPK pathway are involved in a fraction of Aroclor 1242-induced activation of PLA(2).

Activation of neutrophil calcium-dependent and -independent phospholipases A2 by organochlorine compounds.

The production of reactive oxygen species by organochlorine pesticides has been implicated in the toxicity and carcinogenicity of these compounds; however, the mechanism by which these agents stimulate the production of oxygen radicals is unknown. Phospholipase A2 (PLA2)-mediated release of arachidonic acid has been shown to play an essential role in superoxide anion (O2-) production in neutrophils exposed to various physiologic and pharmacologic agents. Therefore, studies were performed to determine if the organochlorine pesticides, lindane and dieldrin, activate neutrophils to produce O2- by a mechanism that requires PLA2. Production of O2- and 3H-AA release increased with similar kinetics and concentration-response relations in neutrophils activated with either dieldrin or lindane. Significant release of 3H-AA was seen in neutrophils stimulated with dieldrin or lindane in calcium-free medium and in the presence of the intracellular calcium chelator BAPTA-AM, suggesting that these agents stimulate a PLA2 that does not require calcium for activation. In addition, both O2- production and 3H-AA release were inhibited in a concentration-dependent manner by BEL, a mechanism-based inhibitor of calcium-independent PLA2. These data suggest that dieldrin and lindane stimulate O2- production by a mechanism that involves PLA2. However, release of 3H-AA was not abrogated completely by BEL nor, in the case of dieldrin, preserved entirely in the absence of calcium. This suggests that more than one isoform of PLA2 is activated by dieldrin and by lindane, and that one isoform is calcium-dependent.

Mercury levels in muscle of two fish species and sediments from the Cartagena Bay and the Ciénaga Grande de Santa Marta, Colombia.

Mercury (Hg) content in sediments and muscle from two fish species were determined in Cartagena Bay and Ciénaga Grande de Santa Marta, an industrialized bay and an unpolluted estuary in the Caribbean coast of Colombia. Sampling was conducted four times during March-November 1996, including both the dry and rainy seasons. Significant differences in Hg concentration were detected both for fish and sediments between the two waterbodies. Hg values ranged from 94 to 10,293 microg/kg dry weight (dw) in sediments from Cartagena Bay and between 20 and 109 microg/kg dw in Ciénaga Grande de Santa Marta. Highest Hg concentrations were observed for the omnivorous species Eugerres plumieri, and lowest concentrations were found in the detritivorous Mugil incilis. High Hg concentrations in sediments of Cartagena Bay were detected in front of the sewage discharge of an extinct chlor-alkali plant, with decreasing concentrations in stations far from the source. Our results suggest that Hg can be persistent in the sediments of previously exposed ecosystems and that the use of their biological resources should be avoided until decontamination programs guarantee safe levels of the metal in the environment.

Quantitative structure-retention relationships of polychlorinated naphthalenes in gas chromatography.

A quantitative structure-retention relationship (QSRR) model has been developed for the gas chromatographic relative retention indices (RRis) of 62 polychlorinated naphthalene (PCN) congeners in a non-polar column, DB-5 (5% phenyl, methylpolysiloxane). Chemical descriptors were calculated from the molecular structures of PCNs and related to their gas chromatographic RRis by multiple linear regression analysis. The proposed model had a multiple square correlation coefficient R2 = 0.995, and standard error SE = 16.7. A QSRR reveals that the gas chromatographic retention of PCNs is associated with the number of chlorine substitutions, influenced by electronic descriptors such as heat of formation, maximum value for atomic valence, and the minimum value for electronic orbital population.

Hyponatremia-associated rhabdomyolysis.

BACKGROUND: Hyponatremia is the most frequent electrolyte disorder. However, hyponatremia rarely results from excessive water intake, unless the kidney is unable to excrete free water, such as in patients on thiazide diuretics; in addition, hyponatremia is an uncommon cause of rhabdomyolysis. METHODS: We present a 51-year-old hypertensive woman on chronic hydrochlorothiazide therapy who developed acute water intoxication and severe myalgias. RESULTS: The patient developed acute hypotonic hyponatremia and subsequent rhabdomyolysis. We discuss the mechanisms responsible for the development of hyponatremia and its association with rhabdomyolysis. CONCLUSION: Muscle enzymes should be monitored in patients with acute hyponatremia who develop muscle pain, and hyponatremia-induced rhabdomyolysis must be considered in patients with myalgias receiving thiazide diuretics.

Mercury in environmental samples from a waterbody contaminated by gold mining in Colombia, South America.

Environmental samples from a marsh, which receives mercury discharges from a gold mine in Colombia (South America), were evaluated for total mercury content. Mercury concentrations were analyzed in sediments, macrophytes and fish species from different trophic levels. The Mean mercury levels in sediments oscillated between 140 and 355 micrograms/kg whereas in the macrophyte Eichornia crassipes levels were between 219 and 277 microgram/kg with practically no interseasonal variations. The mercury content in the muscle of fish varied depending on the position in the trophic chain and the feeding habits of each species, oscillating between non-detectable (< 7.4 microgram/kg) and 1084 micrograms/kg. Seasonal variations were only observed in fish species whose habitats are mostly the bottom sediment. The presence of mercury in some fish appeared to be the result of bioaccumulation rather than a biomagnification processes. This was clearly evidenced in the detritivorous species Triportheus magdalenae which obtain their food within the sediments and whose mercury concentrations were significantly higher when compared to the other species including carnivorous. The relatively low mercury concentrations found in fish may be due to both the dispersion of the contaminant once it reaches the waterbody and the migrational characteristics of the fish species.

Glomerulomegaly and proteinuria in a patient with idiopathic pulmonary hypertension.

Glomerulomegaly is a histologic finding present in idiopathic pulmonary hypertension, congenital cyanotic heart disease, morbid obesity associated with sleep apnea syndrome, sickle cell disease, and polycythemic states. This study examines the case of a 34-yr-old woman with idiopathic pulmonary artery hypertension who presented with nephrotic-range proteinuria. Kidney biopsy revealed enlarged glomeruli with mesangial-proliferative glomerulonephritis. A review of the pertinent literature and a discussion of the proposed pathophysiologic mechanisms leading to glomerulomegaly are presented.

Molecular structure and gas chromatographic retention behavior of the components of Ylang-Ylang oil.

Using quantitative structure-retention relationships (QSRR) methodologies the Kovats gas chromatographic retention indices for both apolar (DB-1) and polar (DB-Wax) columns for 48 compounds from Ylang-Ylang essential oil were empirically predicted from calculated and experimental data on molecular structure. Topological, geometric, and electronic descriptors were obtained for model generation. Relationships between descriptors and the retention data reported were established by linear multiple regression, giving equations that can be used to predict the Kovats indices for compounds present in essential oils, both in DB-1 and DB-Wax columns. Factor analysis was performed to interpret the meaning of the descriptors included in the models. The prediction model for the DB-1 column includes descriptors such as Randic's first-order connectivity index (1X), the molecular surface (MSA), the sum of the atomic charge on all the hydrogens (QH), Randic's third-order connectivity index (3X) and the molecular electronegativity (chi). The prediction model for the DB-Wax column includes the first three descriptors mentioned for the DB-1 column (1X, MSA and QH) and the most negative charge (MNC), the global softness (S), and the difference between Randic's and Kier and Hall's third-order connectivity indexes (3X-3XV).