Effect of whole and fractionated intravenous immunoglobulin on complement in vitro

Intravenous immunoglobulins (IVIG) are increasingly used for treatment of inflammatory diseases, and the modulation of complement may contribute to some of its beneficial effects. IVIG may bind C1q and activated C3 and C4, and enhance inactivation of C3b. We have previously shown that IVIG inhibited complement-mediated lysis solely via its Fc part through interaction with the classical pathway. In the present study we have investigated whole IVIG (Octagam, and Sandoglobulin) and the monomer, dimer and multimer fractions of Octagam with respect to complement activation in serum and inhibition of complement lysis of red cells. The isolated fractions were found to be stable, homogeneous (monomer, dimer or multimer) and pure (virtually only IgG). Both whole IVIG and its fractions significantly activated complement in serum and inhibited hemolysis compared with human albumin. These effects were most pronounced in the monomer, less in the multimer and least in the dimer fraction. The complement activation was shown to be mediated through the classical pathway since formation of C1rs-C1inh complexes and C4bc were increased, in contrast to Bb. Surprisingly, heat aggregation of Octagam was not followed by a corresponding increase in complement activation, as would be expected, unless it was dialysed before heating, suggesting that it is stabilized to avoid excess activation. In conclusion, the results support the hypothesis that IVIG causes a mild activation of complement in vitro. We suggest that this effect may contribute to the complement inhibitory properties of IVIG by diverting complement deposition from the target to the fluid phase.     

Survival on renal replacement therapy in Europe: is there a 'centre effect'?

OBJECTIVE: Survival is the ultimate outcome measure in renal replacement therapy (RRT) and may be used to compare performance among centres. Such comparison, however, is meaningless if the influences of comorbidity, age and early deaths are not considered. We therefore studied survival rates on RRT in seven centres in Europe after taking into account the influence of age, early deaths, primary renal diagnoses, and comorbidity. DESIGN: A retrospective survival analysis was carried out on 1407 patients who commenced RRT in seven centres across five European countries during a 7-year period. Patients were stratified into low-, medium- and high-risk groups based mainly on comorbidity and to a lesser extent on age at commencement of RRT. Kaplan-Meier survival and Cox's proportional hazards model were used to compare survival. RESULTS: Before risk stratification overall 2-year survival across the seven centres ranged from 60.2 to 85.3% (69.3-89.9%) after excluding early deaths) masking a range of survivals of 27.4% for the high-risk group with the worst survival to 100% in the low-risk group with the best survival. After excluding early deaths 2-year survival in the low risk groups (n=622) was greater than 90% in all centres. Multivariate analysis showed that the mortality risk increased four fold from low- to medium- and a further 1.6-fold from medium- to high-risk group. However, despite this adjustment for comorbidity and age there still remained a significant difference in survival among some centres, i.e. a 'centre effect' which ranked the centres. CONCLUSION: Risk stratification diminishes the variance in survival between centres but a centre effect remains despite adjusting for age and comorbidity. Multicentre prospective studies are urgently required to identify the reasons for this apparent centre effect.     

Body composition at farrowing and nutrition during lactation affect the performance of primiparous sows: II. Milk composition, milk yield, and pig growth

We used 35 primiparous sows to investigate the link between body fatness at farrowing and voluntary feed intake (VFI) during lactation. Two groups of sows were fed differently throughout gestation (either 2.3 kg/d of a diet containing 5.8% CP and 14.6 MJ DE/kg as fed or 1.7 kg/d of a diet containing 15.6% CP and 14.5 MJ DE/kg as fed) so that they commenced lactation at a similar body weight (158 to 152 kg) but with different body compositions: either 340 (fat) or 280 (lean) g of body fat/kg BW (P < .001). During lactation, sows were offered either a low-protein diet (7.9% CP and 15.5 MJ DE/kg as fed) or a high-protein diet (19.0% CP and 15.6 MJ DE/kg as fed) on an ad libitum basis. During lactation, VFI was measured daily, and sow body weight and backfat were measured weekly. Blood samples were collected from sows on d 110 of gestation and d 14 and 28 of lactation, and plasma was analyzed for NEFA, glycerol, insulin, glucose, and beta-hydroxybutyrate. Fat sows ate 30% less than their lean counterparts during lactation (P < .001), which corresponded to a 70% higher concentration of NEFA in plasma (P = .01) and a 30% higher concentration of glycerol (P = .15). The VFI during the first 2 wk of lactation was affected only by body fatness and not by the protein content of the lactation diet. The dietary supply of protein influenced VFI during wk 3 and 4 of lactation, possibly by affecting milk production and hence the drive to consume feed. Weight loss, particularly lean tissue loss, was minimized by feeding the high-protein diet during lactation (P < .002).     

Removals of hydrogen peroxide and hydroxyl radical by thiol-specific antioxidant protein as a possible role in vivo

Thiol-specific antioxidant protein (Protector Protein; PRP) from Saccharomyces cerevisiae was found to remove hydrogen peroxide and hydroxyl radical in the presence of dithiothreitol (DTT). Without DTT as a reducing equivalent, the antioxidant protein did not show the activities for destroying hydrogen peroxide and hydroxyl radical. N-ethylmaleimide (NEM) was observed to prevent the PRP from both removing hydrogen peroxide and protecting the cleavage of DNA. These observations suggest that the sulfhydryl of cysteine in PRP could function as a strong nucleophile to attack and destroy H2O2 and .OH.     

Trimucytin: a collagen-like aggregating inducer isolated from Trimeresurus mucrosquamatus snake venom

OBJECTIVE: This study tested the hypothesis that gut stasis induced by parenteral morphine sulfate (MS) leads to enhanced bacterial translocation in rats on total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: TPN and MS are common adjuncts in the care of critically ill patients. TPN is known to provoke a variable degree of translocation. MS induces gut stasis with an accompanying bacterial overgrowth. The effect of these two treatments in combination on translocation is not known. METHODS: Rats were provided with central and subcutaneous lines for the continuous infusion of nutrients and drugs, respectively. Intestinal transit was assessed by the caudal movement of a fluorescent marker intubated into the proximal duodenum. Quantitative bacteriology was carried out from various segments of the gut and from ileocecal mesenteric lymph nodes (MLN), spleen, liver, and systemic blood obtained by cardia puncture on sacrifice at 96 hours. RESULTS: Transit was unchanged by TPN alone but prolonged when given in combination with MS. Bacterial overgrowth was also enhanced by MS and increased the bacterial translocation to MLN from 50% of animals with TPN, to 100% in those receiving both TPN and MS; the colony-forming units per MLN increased from 33 +/- 14 with TPN alone to 2079 +/- 811 (STD) with TPN plus MS. Furthermore, no bacteria were found at systemic sites with TPN alone, but in 93.3% of animals receiving TPN and MS. In a subgroup of rates provided with glutamine in TPN, the TPN plus MS effects on translocation were not reversed. CONCLUSIONS: These observations demonstrate the important role that morphine plays in promoting translocation, presumably by disrupting fasting motility and enhancing bacterial overgrowth.     

Trauma-hemorrhage causes prolonged depression in cellular immunity

The intravenous immunotherapy with high-dose interleukin-2 (IL-2) would constitute one of the most effective treatments of metastatic renal cell carcinoma (RCC). More recently, IL-2 subcutaneous therapy has also appeared active, either alone or in association with interferon, with results comparable to those found with the intravenous route of injection, but with a lower toxicity. On this basis, we have designed a protocol of treatment with low-dose IL-2 alone given subcutaneously as a first or a second line therapy in metastatic RCC. The study included 60 consecutive patients (pts) (M/F: 39/21, median age 56 years, range 26/74). IL-2 was given at a dose of 3 millions IU twice/day for 5 days/week, for 6 weeks, corresponding to one cycle. In non progressed pts a second cycle was repeated after a 28-day rest period. Dominant metastasis sites were, as follows: soft tissues: 8; bone: 11; lung: 29; liver: 3; liver plus lung: 7; adrenal: 2. The minimum follow-up was 18 months and the median follow-up was 34 months (range 18-48). A complete response (CR) was achieved in 2/60 (3%) pts. A partial response (PR) was obtained in 15/60 (25%). Therefore, tumor objective rate (CR + PR) was 17/60 (28%). The median duration of response was 13 months (4-33).(ABSTRACT TRUNCATED AT 250 WORDS)     

Flexible cystoscopy during urodynamic evaluation of spinal cord-injured patients

Eighty-one consecutive flexible cystoscopic examinations were performed on 69 patients with spinal cord injury (SCI) at the time of their urodynamic study. The indications for cystoscopy included hematuria, recurrent urinary tract infections, symptoms of bladder outlet obstruction, the presence of an intraurethral sphincter stent requiring evaluation, neurogenic vesical dysfunction requiring endourodynamic study (cystometrogram through the working port of the flexible cystoscope), or bladder calculi. Flexible cystoscopy was accomplished in all patients, whether lying supine or seated in a wheelchair (N = 16). Only 6 of 39 patients with previous episodes of autonomic dysreflexia became hypertensive during cystoscopy. When a urodynamic catheter could not be inserted, the flexible cystoscope was particularly useful in defining the urethral anatomy or obstruction and in performing endourodynamic evaluation. The only complication was the development of febrile urinary tract infection in four patients. The flexible cystoscope is a valuable tool in the urodynamic laboratory caring for patients with SCI and is effective for use in endourodynamics, especially when patient positioning or catheter placement is difficult. The procedure is well tolerated, causes minimal stimulation leading to the development of autonomic dysreflexia, and provides accurate cystometric data.     

Sex hormones, body fat distribution, resting metabolic rate and glucose-induced thermogenesis in premenopausal obese women

The topographic specificity of upper body obesity is known to be at the origin of a series of metabolic complications. In contrast to this negative effect, women with abdominal obesity usually can lose more body weight than women with gluteal-femoral obesity. In order to find some contributive explanations for this effect, we studied resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) in both types of obesity. Since upper body obesity is characterized by androgen excess, a relationship between body fat distribution, sex hormones, RMR and indices of thermogenesis was studied. Of 39 obese women who were recruited (mean age: 32.4 +/- 9.3 years), 30 were compared for analysis. Upper body obesity (waist-to-hip ratio (WHR): 0.84 +/- 0.02; body mass index (BMI) 36.2: 36.2 +/- 6.0) is not characterized by differences in RMR, whereas glucose-induced thermogenesis is significantly higher in this subgroup (P < 0.008), expressed as percentage increase above RMR (18.3 +/- 8.5 vs. 11.9 +/- 3.6%) or as percentage of metabolisable energy intake (8.2 +/- 3.3 vs. 5.8 +/- 2.3%). Correlation coefficient data show that GIT determinants are closely related to WHR (r = 0.43; P < 0.01) and not to BMI. Resting metabolic rate, both in absolute terms and corrected for fat-free mass (FFM), is not related to indices of androgenicity, but is negatively related to serum oestradiol levels; this negative relationship with oestradiol disappears when RMR is corrected for both fat mass (FM) and FFM. GIT parameters are not related to free testosterone or oestradiol, regardless of the phase of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of postpartum and nonpostpartum depression: clinical presentation, psychiatric history, and psychosocial functioning

This study compared a sample of postpartum women diagnosed with depression with a nonpostpartum depressed group and 2 nondepressed control groups. Women's depressive episodes were compared to determine whether differences existed in symptomatology, previous history, or course. Results indicate that postpartum depression tends to be relatively mild. Both depressed groups had high rates of positive psychiatric history and were equally likely to have recovered at a 6-month follow-up. Groups were also compared on psychosocial variables known to covary with depression: interpersonal relations, stress, and coping. A series of multivariate analyses of covariance showed few differences between the depressed groups that were not attributable to symptom severity, although postpartum depressed women did report better marital relations than did the nonpostpartum depressed women. These findings suggest that there is little to distinguish postpartum from nonpostpartum depression beyond differences in symptom severity.