Salvage of patients with relapsed and refractory Hodgkin disease (HD) with highdose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dosedense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .
Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide ( ⅐ NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in ⅐ NO scavenging reactions. All hemoglobins studied exhibited a value of 30 M ؊1 s ؊1 for both ⅐ NO bimolecular association rate constants and the rate constants for ⅐ NO-induced oxidation in vitro. Only the ⅐ NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter ⅐ NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of ⅐ NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.Control of blood pressure and resistance to blood flow is achieved by a dynamic constriction and relaxation of smooth muscle tissue which surrounds all blood vessels except capillaries. Vascular smooth muscle tension is continually adjusted by a complex system that causes either vasoconstriction or vasodilation, depending on metabolic need (1). Research performed over the last decade has established that endotheliumderived nitric oxide ( ⅐ NO) 1 can cause vasodilation. ⅐ NO is produced by endothelial cells that lie between the intravascular space and the surrounding smooth muscle. Among the findings was the demonstration that ⅐ NO donors (e.g. nitroprusside, nitroglycerin) lead to vasorelaxation through activation of guanylate cyclase, whereas inhibitors of ⅐ NO synthesis (e.g. N Gmonomethyl-L-arginine) or scavengers (e.g. hemoglobin) cause vasoconstriction (for reviews, see Refs. 2 and 3).Since cell-free hemoglobin is being developed as a red cell substitute (4), reactions between hemoglobin and ⅐ NO are of potential importance in maintenance of microvascular blood flow and O 2 delivery. Despite the wide variation that exists in the physical properties (O 2 affinity, molecular mass, and solution properties) of different cell-free hemoglobins, it appears vasoconstriction is a feature common to many hemoglobin solutions (for reviews, see Refs. 2, 3, and 5). It is tempting to conclude that ⅐ NO scavenging is the principal, if not sole mechanism for vasoconstriction associated with cell-free hemoglobin. However, it is well established that multiple factors contribute to the physiological control of vascular smooth muscle to...
We have compared polyethylene glycol-modified bovine hemoglobin (PEG-Hb; high O2 affinity, high viscosity, high oncotic pressure) and human hemoglobin cross-linked between the alpha-chains (alpha alpha-Hb; low O2 affinity, low viscosity, low oncotic pressure) with a non-O2-carrying plasma expander (pentastarch, high viscosity and oncotic pressure) after a 50% (by volume) exchange transfusion followed by a severe (60% of blood volume) hemorrhage. Mean arterial pressure and systemic vascular resistance rose significantly in the alpha alpha-Hb but not in the PEG-Hb animals. Two-hour survival was greater in the PEG-Hb animals (93%) than in control (35%), pentastarch (8%), or alpha alpha-Hb (6%) animals. In the PEG-Hb animals, there was no disturbance of acid-base balance, significantly less accumulation of lactic acid, and higher cardiac output than in the other groups. The data suggest that the rise in vascular resistance that follows alpha alpha-Hb exchange transfusion offsets the additional O2 transport provided by the cell-free hemoglobin. When resistance does not rise, as with PEG-Hb, even relatively small amounts of cell-free hemoglobin appear to be a very effective blood replacement.
Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed.
We have measured plasma volume and cardiac index in rats after 50% isovolemic exchange transfusion with human hemoglobin cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) and with bovine hemoglobin modified with polyethylene glycol (PEGHb). alpha alpha Hb and PEGHb differ in colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb-treated animals were significantly elevated (74.0 +/- 3.5 ml/kg) compared with animals treated with alpha alpha Hb (49.0 +/- 1.2 ml/kg) or Ringer lactate (48.0 +/- 2.0 ml/kg) or with controls (58.2 +/- 1.9 ml/kg). Heart rate reduction after alpha alpha Hb exchange is opposite to that expected with blood volume contraction, suggesting that alpha alpha Hb may have a direct myocardial depressant action. The apparently slow elimination of PEGHb during the 2 h after its injection is a consequence of plasma volume expansion: when absolute hemoglobin (concentration x plasma volume) is compared for PEGHb and alpha alpha Hb, no difference in their elimination rates is found. These studies emphasize the need to understand blood volume regulation when the effects of cell-free hemoglobin on hemodynamic measurements are evaluated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.