Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.     

Atrial fibrillation. The therapeutic options

Atrial fibrillation (AF) is a common cardiac arrhythmia which is particularly prevalent among the elderly. In patients with AF of recent onset, restoration of sinus rhythm may be feasible and this can be achieved by DC cardioversion, or by the use of one of a number of drugs including amiodarone, flecainide or propafenone. Neither digoxin nor the calcium antagonists facilitate the restoration of sinus rhythm. Recurrence of AF is common after successful cardioversion and, although long term antiarrhythmic drug therapy may help to maintain sinus rhythm, all such drugs are potentially toxic and can have important proarrhythmic actions. In patients with chronic AF, restoration of sinus rhythm is rarely possible and treatment is directed towards control of the ventricular response rate, which may be achieved with digoxin and/or a rate-limiting calcium antagonist such as verapamil or diltiazem; beta-blockers may also be used although they appear to impair effort tolerance. In addition, long term anticoagulation may be indicated to reduce the risks of systemic embolisation, even in patients with 'nonrheumatic' AF; antiplatelet drugs are of no apparent value in this context. A minority of patients present with AF associated with ventricular pre-excitation; in these individuals both digoxin and the calcium antagonists are contraindicated and the ventricular response rate should be controlled with flecainide, amiodarone or propafenone.     

The allergens of Epicoccum nigrum Link. I. Identification of the allergens by immunoblotting.

Two atmospheric isolates of Epicoccum nigrum (EN) were grown under sporulation conditions. Dialyzed extracts of spores, (greater than 95% pure) and pure mycelia were used for skin testing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting. By skin testing, 49 of the 126 atopic patients were found to be sensitive to EN in St. Louis, Mo., and Corpus Christi, Texas, combined. On immunoblotting, which was performed on 17 sera, 44 bands (12.3 to 119.0 kd) were detected; six were unique to spore, four were unique to mycelium, and 34 were common to both. No single band bound IgE from all sera. The most frequent band corresponding to 42 kd occurred in 11 sera. Five other bands were recognized by more than one half, whereas the remainder bound fewer sera. All skin test-positive patients had positive immunoblots; the number of bands recognized varied from three to 25. Spore or mycelium-specific, as well as common bands were recognized by 13 of 17 sera. Two sera recognized only spore and mycelium-specific bands. Only spore-specific bands were bound by two sera. No strain differences were detected. The binding patterns were comparable in the sera from both St. Louis, Mo., and Corpus Christi, Texas. These data suggest that EN is a significant allergen in urban communities. Allergenic proteins occur in both spore and mycelium, suggesting that both must be included in the reagents for skin testing and immunotherapy.     

Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate)

Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-d-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60–70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.     

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.     

LONG-TERM OUABAIN ADMINISTRATION DOES NOT ALTER BLOOD PRESSURE IN CONSCIOUS SPRAGUE-DAWLEY RATS

1. We tested the ability of ouabain to cause chronic hyper tension by continuously infusing ouabain for 28 days (mini-osmotic pump implantation; i.p.). The blood pressure and metabolic effects of sham (150 mmol/L NaCI; n= 12) or ouabain infusion (10 μg/kg per day; n= 14; 100 μg/kg per day; n = 14) were examined in conscious Sprague-Dawley rats. 2. Plasma ouabain concentrations measured after 28 days of ouabain infusion were as follows: sham, not detectable (n= 11); ouabain 10 μg/kg per day, 0.60 ± 0.07 nmol/L (n= 14); and ouabain 100 μg/kg per day, 7.17 ± 0.57 nmol/L (n= 14; P < 0.001). 3. Sham or ouabain infusion did not alter food intake, bodyweight, water intake or urine output in conscious rats. 4. Blood pressure was not altered by sham treatment. Ouabain at 10 μg/kg per day or 100 μg/kg per day did not produce consistent rises in blood pressure. Ouabain at 10 μg/kg per day increased blood pressure on treatment day 12 only (+ 6mmHg; P < 0.05), while at 100μg/kg per day blood pres sure increased on treatment days 16 (+ 9 mmHg; P < 0.05) and day 18 (+ 8mmHg; P < 0.05) only. There was no significant difference in blood pressure between sham and ouabain groups. 5. Renal blood flow was decreased in rats infused with ouabain at 10 μg/kg per day (2.0 ± 0.3 mL/min per 100 g body-weight; n= 5; P < 0.01) and 100 μg/kg per day (2.2 ± 0.4 mL/ min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (3.5 ± 0.2 mL/min per 100 g bodyweight; n= 6). Renal vascular resistance was increased in rats treated with ouabain at 10 μg/kg per day (65.5 ± 12.6 mmHg/mL per min per 100 g bodyweight; n= 5; P < 0.01) and 100 μg/kg per day (66.0 ± 15.6 mmHg/mL per min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (32.6 ± 2.5 mmHg/mL per min per 100 g bodyweight; n= 6). 6. High plasma concentrations of ouabain do not cause consistent increases in blood pressure in conscious Sprague-Dawley rats.     

Evaluating food fortification options: general principles revisited with folic acid.

OBJECTIVES. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. METHODS. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. RESULTS. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. CONCLUSIONS. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply.