Changes of plasma volume and plasma composition in water-deprived rats

Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.     

Failure of averaging in the construction of a conductance-based neuron model

Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.     

The effect of amiloride on sodium and potassium fluxes in red cells

1. The effect of amiloride on the influx and efflux of (24)Na and (42)K in red cells was studied. The drug was added to the bathing Ringer or else incorporated in resealed ghosts.2. Amiloride does not inhibit the active or the passive (ouabain insensitive) extrusion of (24)Na.3. Amiloride inhibits the influx of (24)Na into red cells by 70%.4. Whether added to the inside or to the outside of the cells amiloride has no effect on the efflux of (42)K.5. Amiloride does not modify the uptake of (42)K from control Ringer. This uptake is strongly inhibited by the removal of Na. Amiloride has no effect on the extent of this inhibition.6. It is concluded that amiloride specifically inhibits the passive penetration of Na, and has no effect on the Na-K-pumping mechanism. However, at the concentration which inhibits 70% of the influx, amiloride fails to produce an observable effect on the ouabain-insensitive Na-efflux.7. On the basis that the information obtained could be extrapolated to other membranes, the effect of amiloride on epithelial membranes is discussed.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.     

Bacterial DNA activates human neutrophils by a CpG-independent pathway

Bacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and dendritic cells in a CpG-dependent manner. In this work we demonstrate that bacterial DNA, but not mammalian DNA, induces human neutrophil activation as assessed by L-selectin shedding, CD11b upregulation, and stimulation of cellular shape change, IL-8 secretion, and cell migration. Induction of these responses is not dependent on the presence of unmethylated CpG motifs, as neutrophil stimulatory properties were neither modified by CpG-methylation of bacterial DNA nor reproduced by oligonucleotides bearing CpG motifs. We found that human neutrophils express Toll-like receptor (TLR) 9 mRNA. However, as expected for a CpG-independent mechanism, activation does not involve a TLR9-dependent signaling pathway; neutrophil stimulation was not prevented by immobilization of bacterial DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of note, both single-stranded and double-stranded DNA were able to induce activation, suggesting that neutrophils might be activated by bacterial DNA at inflammatory foci even in the absence of conditions required to induce DNA denaturation. Our findings provide the first evidence that neutrophils might be alerted to the presence of invading bacteria through recognition of its DNA via a novel mechanism not involving CpG motifs.     

Is choledochoduodenostomy in the treatment of stones in the common bile duct an obsolete technique?

The complex pathogenesis of bile duct stones, the anatomical properties of the biliary tree, the patient's age, associated diseases, as well as the technical devices available, may explain the great variety of procedures and preferences of different groups in the treatment of choledocholithiasis. Since no technique is infallible or free of complications, it seems unfair to argue that procedures whose efficacy has been proven by many authors are obsolete. This is the case of choledochoduodenostomy (CDS) in the treatment of common bile duct (CBD) stones. The complications associated with CDS, (ascending cholangitis, and sump syndrome) have been overemphasized and have led CDS to be rejected by many surgeons. Our experience with this technique is good and concurs with that of Madden and others.Data on 125 patients with CBD stones treated with CDS between 1968 and 1982 are analyzed. Sixty-eight of them were female and the mean age was 61.4 years; 73.6% were more than 50 years old. There were frequent accompanying diseases, especially cardiovascular ones. More than half of the patients had a previous operation on the biliary tree. The duct diameter was always greater than 20 mm and it was frequently associated with stenosis of the distal choledochus. Floercken's technique of CDS was the most frequently used, after Kocher's maneuver had been performed. There was no intraoperative mortality. Postoperative mortality was 3.2% and is analyzed in detail. The incidence of postoperative complications was 42.4%. Most were septic complications or those ascribed to accompanying diseases. Late operative cholangitis was present in 1.6% of patients, comparable with reports of other authors. We encourage the use of CDS in the treatment of CBD stones provided that: (a) careful attention is paid to its clinical indications, considering that the patient may benefit from alternative techniques, for example, duodenoscopic papillotomy; and (b) choledochal dilatation is greater than 20 mm in diameter and the choledochal and duodenal walls are normal. We specifically recommend CDS as the primary operation for patients with choledochal funnel syndrome. The operation is simple, restores normal digestive function, and almost always resolves the problems of CBD stones in high-risk patients.

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Resumen La compleja patogenia de los cálculos del colédoco, las propiedades anatómicas del árbol biliar, la edad del paciente, las patologías asociadas y otros factores, junto con la disponibilidad de diversos elementos técnicos, explican la gran variedad de procedimientos y de preferencias por parte de los cirujanos en el tratamiento y de preferencias por parte de los cirujanos en el tratamiento de la litiasis biliar. Puesto que ninguna técnica operatoria es infalible ni totalmente libre de complicaciones, parece injusto argumentar que procedimientos cuya eficacia ha sido comprobada por muchos autores sean calificados como obsoletos. Tal es el caso de la coledocoduodenostomía (CDS) en el tratamiento de los cálculos del colédoco. Las complicaciones asociadas con la CDS (colangitis ascendente y el sindrome del segmento distal ciego) han sido exageradas, lo cual ha llevado a muchos cirujanos a rechazar la CDS. Nuestra experiencia con esta técnica es buena y está de acuerdo con la de Madden y de otros. Se analizaron los datos en 125 pacientes con cálculos del colédoco tratados con CDS entre 1968 y 1982. Sesenta y ocho eran mujeres y la edad promedio fué de 61.4 años; 73.6% eran mayores de cincuenta años. Otras enfermedades asociadas fueron halladas con frecuencia, especialmente las cardiovasculares. Más de la mitad de los pacientes tenían historia de una operación previa sobre el árbol biliar. El diámetro del colédoco fué superior a 20 mm en todos los casos y con frecuencia se encontró estenosis árbol de la porción distal. La técnica de Floercken fué la más frecuentemente utilizada, una vez realizada la maniobra de Kocher. No hubo mortalidad intraoperatoria. La mortalidad postoperatoria fué de 3.2% y se analiza en detalle. La tasa de complicaciones postoperatorias fué de 42.4%, incluyendo las sistematicas y las locales, leves y severas, habiéndose observado predominancia de las complicaciones sépticas y de aquellas relativas a patologiás asociadas. La colangitis operatoria tardía ocurrió en el 1.6% de los pacientes, tasa comparable a la informada por otros autores. Nosotros preconizamos el uso de la CDS en el tratamiento de los cálculos del colédoco siempre que: (a) se preste atención cuidadosa a sus indicaciones clínicas, considerando que el paciente puede beneficiarse con otras alternativas, por ejemplo la papilotomía duodenoscópica; y (b) la dilatación del colédoco sea de un diámetro superior a 20 mm y que las paredes tanto del colédoco como del duodeno sean normales. Específicamente recomendamos la CDS como la operación primaria para pacientes con el síndrome del embudo coledociano (estenosis distal con dilatación proximal). La operación es sencilla, restaura la función digestiva normal y en forma casi uniforme resuelve los problemas que producen los cálculos del colédoco en pacientes de alto riesgo.

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Résumé La pathogénie complexe de la lithiase biliaire, les caractères anatomiques des voies biliaires ainsi que l'âge des malades, les affections associées et la grande variété des méthodes techniques expliquent la grande diversité des procédés de traitement de la lithiase choledocienne employés par les différentes équipes chirurgicales. Aucune technique n'étant infaillible ou exempte de complications, il paraît inconsidéré d'abandonner toute méthode qui a fait ses preuves. Il en est ainsi de la choledocoduodénostomie. Les complications attribuées à ce type d'intervention comme l'angiocholite ascendante, et le syndrome du moignon sous-anastomotique ont été exagérées conduisant de nombreux chirurgiens à l'écarter de leur pratique. Notre expérience de la choledocoduodénostomie est bonne et coincide avec celle de Madden et d'autres auteurs. Les données recueillies chez 125 malades qui présentaient des calculs de la V.B.P. et qui furent traités par la choledocoduodénostomile de 1968 à 1982 ont été étudiées. Soixante-huit étaient des femmes. La moyenne d'âge était de 61.4 ans, 73.6% étaient âgés de plus de 50 ans. Les affections associées étaient fréquentes en particulier les affections cardiovasculaires. Plus de la moitié de nos opérés avaient déjà subi une intervention sur la voie biliaire. Le diamètre de la voie biliaire a toujours été supérieur à 20 mm et la dilatation se trouvait souvent au dessus d'un rétrécissement du bas cholédoque. La technique de Floercken fut le plus souvent employée après le décollement du bloc duodénopancréatique. Il n'y eu aucun décès peropératoire. La mortalité postopératoire s'est élevée à 3.2% et a été étudiée avec précision. Le taux des complications postopératoires a atteint 42.4%, dont les infections et les désordres secondaires aux affections associées occupent la première place. Le taux de l'angiocholite postopératoire tardive s'est élevé à 1.6%, identique à celui rapporté par d'autres auteurs. Notre expérience nous permet de recommander la choledocoduodénostomie à condition (a) d'apporter une attention particulière aux indications après avoir pris en considération la possibilité de traiter la lithiase par une autre méthode, la sphinctérotomie endoscopique par exemple; et (b) de la réserver aux cas où le diamètre de la V.B.P. est supérieur à 20 et ou les parois de la voie biliaire et du duodénum sont normales. Nous considérons qu'elle est particulièrement indiquée en présence du syndrome du cholédoque en entonnoir. L'intervention est simple, restaure la fonction digestive normale et résoud le problème des calculs de la V.B.P. chez les malades de haut risque.