Rise In C-reactive Protein Research Articles

Classification and early recognition of gastric conduit failure after minimally invasive esophagectomy

Esophagectomy is a high-risk procedure, with significant morbidity resulting from gastric conduit failure. Early recognition and management of these complications is essential. This study aimed to investigate the clinical value of routine investigations after minimally invasive esophagectomy (MIO) and to propose a classification system for gastric conduit failure. For esophagogastric resection, MIO is the procedure of choice in the authors' unit. Standard postoperative care similar to that for open esophagectomy is undertaken on a specialist ward. Routine investigations include daily assessment of C-reactive protein (CRP), white cell count (WCC), and a contrast swallow on postoperative day (POD) 5. The authors performed a retrospective analysis to assess the utility of these tests. Of a prospective cohort of 50 patients from April 2004 to July 2006, 26 (52%) had an uneventful recovery (U), 24 (48%) experienced complications (C) of varying nature and severity, and 1 died (2%). All the patients demonstrated a transient abnormal rise in CRP until POD 3. In group U, the levels then fell, but in group C, they remained elevated (POD 5: U = 96, C = 180; p < 0.01). This discrepancy trend was further exaggerated in the nine patients with gastric conduit failure (POD 5: GC = 254; p < 0.01), whereas contrast swallow failed to identify this complication in six patients. Simple anastomotic leaks (type 1, n = 4) were managed conservatively. Patients with conduit tip necrosis (type 2, n = 3) and complete conduit ischemia (type 2, n = 2) were managed by repeat thoracotomy and either refashioning of the conduit or take-down and cervical esophagostomy. None of the patients with conduit failure died. Postoperative CRP monitoring is a highly effective, simple method for the early recognition of gastric conduit failure. This new system of classification provides a successful guide to conservative management or revisional surgery.

Risk factors for negative blood cultures in adult medical inpatients – a retrospective analysis

BackgroundThe identification of clinical factors associated with negative blood cultures could help to avoid unnecessary blood cultures. C-reactive protein (CRP) is a well-established inflammation marker commonly used in the management of medical inpatients.MethodsWe studied the association of clinical factors, CRP levels and changes of CRP documented prior to blood culture draws with the absence of bacteremia for hospitalized medical patients.ResultsIn the retrospective analysis of 710 blood cultures obtained from 310 medical inpatients of non-intensive-care wards during one year (admission blood cultures obtained in the emergency room were excluded), the following retrospectively available factors were the only independent predictors of blood cultures negative for obligate pathogens: a good clinical condition represented by the lowest of three general nursing categories (OR 4.2, 95% CI 1.8 – 9.5), a CRP rise > 50 mg/L documented before the blood culture draw (OR 2.0 95% CI 1.8–9.5) and any antibiotic treatment in the previous seven days (OR 2.0, 95% CI 1.1–3.5).ConclusionIncluding the general clinical condition, antibiotic pre-treatment and a substantial rise of CRP into the decision, whether or not to obtain blood cultures from medical inpatients with a suspected infection, could improve the diagnostic yield.

Lymphoid follicles in joints: What do they mean?

The existence of lymphoid follicles in the synovium of patients with inflammatory arthritis, including the feature we now recognize as a germinal center of proliferating B cells, has been known since the nineteenth century (1). It has also long been recognized that these structures are present in only a minority of cases and are not specific to rheumatoid disease. Most of the lymphocytes seen in synovium are T cells (2), although this analysis does not include B cell–derived plasma cells, which can be very numerous. Perhaps surprisingly, we are still faced with the question: are these B cell–containing follicles telling us something important about the disease and how to treat it, or are they a secondary curiosity? We have probably learned enough about inflammatory arthritis to know that the answer will lie somewhere in between and that every patient may be slightly different. Nevertheless, careful studies, such as the one by Thurlings and colleagues reported in this issue of Arthritis & Rheumatism (3), may reveal broad truths that may at least guide useful treatment strategies. As is often the case, the study by Thurlings et al is most interesting for what was not found. It confirms the historical belief that organized collections of B cells occur in rather few rheumatoid arthritis (RA) synovia. Moreover, it shows that, at least in terms of measures in the Disease Activity Score 28-joint assessment (4), such as the numbers of swollen and tender joints, amount of bone damage, and presence of rheumatoid nodules, lymphoid neogenesis does not seem to determine disease phenotype. It is difficult to escape the conclusion that B cells in joints may not be that important. Should we be surprised? Probably not, since the role of B cells is not usually at a site of inflammation itself. The findings of van Boxel and Paget (2) (T cell predominance) apply to more or less all inflammation. B cells normally contribute to inflammation either by generating plasma cells, which, in lymphoid tissue or at sites of inflammation, secrete antibodies capable of activating inflammatory mechanisms, or by presenting antigen to T cells in draining lymph nodes so that primed T cells can recirculate to inflamed tissue. Starting with antibody production, arguably the most interesting finding reported by Thurlings and colleagues is that the presence of organized B cell collections in synovium was not correlated with the presence of detectable autoantibodies (rheumatoid factor and antibodies against citrullinated proteins). The implication is that if autoantibodies contribute to inflammation through the interaction of immune complexes with macrophage Fc receptors and complement, then in many cases the B cells responsible are to be found largely or wholly in lymph nodes or spleen. This is consistent with the body of data indicating that autoantibody production frequently precedes any clinical sign of cellular infiltration of synovium by up to several years (5). (Interestingly, preclinical autoantibody production can be associated with a rise in C-reactive protein [CRP] levels, suggesting that immune complexes may drive an acute-phase response, perhaps by Kupffer cell activation, without causing inflammation.) It does not, of course, imply that therapies targeting B cells should not be designed to reach synovial B cell collections as well as those elsewhere. But it does tend to imply that this is not the primary objective. In terms of antigen presentation, the prima facie Jonathan C. W. Edwards, MD, Maria J. Leandro, MD, PhD: University College London, London, UK. Dr. Edwards has received honoraria (less than $10,000) from Roche. Dr. Leandro has received consulting fees, speaking fees, and honoraria (more than $10,000) from Roche. Address correspondence and reprint requests to Maria J. Leandro, MD, PhD, Room 317, Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK. E-mail: maria.leandro@ucl.ac.uk. Submitted for publication January 11, 2008; accepted in revised form February 29, 2008. Arthritis & Rheumatism

Cytokine responses following laparoscopic or open pyeloplasty in children

The present study evaluated the cytokine response in children following laparoscopic pyeloplasty (LP) or open pyeloplasty (OP). A series of cytokines were measured postoperatively, including interkin1-beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). A total of 31 patients, with an average age of 9.1 +/- 3.0 years (range 2.5-14 years) were studied. Fourteen patients underwent LP and 17 underwent OP. Blood serum concentrations of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, and CRP were measured via enzyme-linked immunosorbent assay (ELISA) before surgery as well as 4, 24, and 48 h following the operation. In addition, the procedure duration, hospital stay, incidence of wound infection, and the recurrence rate of stenosis in both groups were compared. Serum IL-6 and CRP concentrations were significantly elevated in both groups at 4, 24, and 48 h relative to preoperative levels. However, the rise in IL-6 and CRP in OP group was significantly more robust than in LP group. No significant changes were observed in serum levels of IL-1beta, IL-8, IL-10, or TNF-alpha in either group. The procedure duration was significantly longer for LP (193.6 +/- 74.7 min, range 120-360 min) versus OP (120.1 +/- 27.5 min, range 90-165 min, p < 0.05), but the hospital stay following LP was shorter (LP group: 5.3 +/- 1.1 days versus OP group: 9.3 +/- 2.1 days, p < 0.05). No severe complications were noted in either group, however, one child experienced wound infection following OP procedure. An incident of recurrent stenosis following the operation occurred in both groups. There was no postoperative morbidity or severe implications at 12 month follow-up in either group. Both OP and LP are safe and effective procedures for the treatment of ureteropelvic junction obstruction in the pediatric population. However, the shorter hospital stay and decreased cytokine response following LP indicates potential benefits over traditional invasive procedures.

A Report on Associations Among Gastric pH, Bleeding, Duodenogastric Reflux, and Outcomes After Trauma

The pathogenesis of multiple organ failure (MOF) in trauma patients may involve the gastrointestinal tract, but its exact origins remain elusive. In a prospective study, the gastric fluid of major torso trauma patients was examined for evidence of duodenogastric reflux and potential gastric injury, and was compared with patient outcomes regarding MOF. Patient samples were collected daily for 4 days by nasogastric tube and analyzed for pH, hemoglobin, and bile acid. Blood was collected for analysis of C-reactive protein (CRP). Outcomes were recorded for the presence or absence of MOF. The results showed that most patients exhibited alkaline gastric contents (pH >/=4.9) and elevated levels of hemoglobin immediately after the trauma. Although non-MOF patients demonstrated a decline of both mean gastric pH and bleeding by day 4, MOF patients maintained significant elevations in pH during this time period. Mean total bile acid levels were increased in all patients, signifying the presence of duodenogastric reflux. However, there were no clear differences in mean bile acid concentrations between MOF and non-MOF patients over time, although MOF patients tended to exhibit higher levels. All patients showed a progressive rise in serum CRP during the first 24 hours after trauma, which was maintained for 4 days. The initial rise in serum CRP in MOF patients was delayed compared with that in non-MOF patients. We conclude that duodenogastric reflux occurs in trauma patients in the first few days after trauma and may contribute to elevated gastric pH and bleeding. Further study is needed to verify whether monitoring the gastric juice of trauma patients during the first several days of hospitalization, for alkaline pH and excessive blood in the gastric lumen, could lead to better assessments of patient status.

Indices of Obesity and Cardiovascular Risk Factors in British Women

Background: Obesity increases cardiovascular risk through effects on blood pressure, lipoproteins, coagulation factors and inflammatory cytokines, but in women variation in fat distribution complicates these relationships. Central (maletype or visceral) obesity confers greater risk than the more generalised (female) type. This is recognised by the metabolic syndrome which employs waist circumference rather than body mass index (BMI). We examined the relationships of several indices of fat distribution with cardiovascular risk factors in a large cohort of UK women. Material and Methods: 13,389 female department store employees aged 30–65 years not receiving exogenous hormones completed a health questionnaire. Their blood pressure, weight, height, waist and hip circumference, serum cholesterol low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, C-reactive protein (CRP) and plasma fibrinogen were measured. Re-sults: There was a progressive rise in blood pressure, total cholesterol, LDL-C, triglycerides, fibrinogen and CRP with age. After adjustment for these age effects, BMI was most closely related to blood pressure, whereas the waist to height ratio (WHTR) correlated more closely with the other risk factors than BMI, waist circumference or waist to hip ratio (WHPR). Conclusions: Inclusion of height in the definition of metabolic syndrome will produce a clearer association between waist circumference and cardiovascular risk factors. Hypertension may be linked to the metabolic syndrome by its association with general obesity rather than specifically by central obesity.

Increase of serum C‐reactive protein is an early indicator of subsequent symptomatic anastomotic leakage after anterior resection

This prospective study investigated the factors which might indicate anastomotic leakage after low anterior resection. Thirty-three patients who underwent anterior resection for rectal carcinoma (n = 32) and severe dysplasia (n = 1), were monitored daily by serum C-reactive protein (CRP) and white blood cell count (WBC) estimations until discharge from hospital. Computed tomography (CT) scans were performed on postoperative days 2 and 7 and the amount of presacral fluid collection was assessed. All patients had a pelvic drain and the volume of drainage was measured daily. The level of the anastomosis was at a median 5 cm (3-12 cm) above the anal verge. There was no 30-day mortality. Nine (27.2%) of the 33 patients developed a symptomatic anastomotic leakage which was diagnosed at a median of 8 days (range 4-14) postoperatively. The serum CRP was increased in patients who leaked from postoperative day 2 onwards (P = 0.004 on day 2; P < 0.001 on day 3-8). The WBC was decreased in preoperatively irradiated patients on days 1-5 (P </= 0.021), with no difference seen between patients with or without leakage. Patients with leakage had a larger presacral fluid collection on CT on day 7 (median 76 ml vs 52 ml; P = 0.016) and a larger increase in the fluid collection between the first and the second CT examinations (28 ml vs 3 ml; P = 0.046). CONCLUSION; An early rise in serum CRP was a strong indicator of leakage. Monitoring of CRP for possible early detection of symptomatic anastomotic leakage is recommended.

Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers*

To determine gender differences in the innate immune response and vascular reactivity during human endotoxemia. Clinical experimental study. University medical center intensive care research unit. Fifteen female and 15 male volunteers. Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. C-reactive protein, leukocytes, and cytokines were measured at regular time intervals as indicators of inflammation. Heart rate and blood pressure were continuously monitored. Forearm blood flow and the responsiveness of forearm vessels to the intrabrachial infusion of norepinephrine (1-3-10-30 ng/min/dL) were measured before and 4 hrs after the administration of endotoxin using venous occlusion plethysmography. Differences were tested with repeated-measures analysis of variance. Females showed a more proinflammatory response to lipopolysaccharide than males, illustrated by a higher rise in C-reactive protein (42 +/- 3 vs. 29 +/- 3 mg/L, p = .002) and more leukocyte sequestration (leukopenia 1.8 +/- 0.1 x 10 vs. 2.4 +/- 0.1 x 10, p = .003). The increase in cytokine levels showed a more proinflammatory pattern in females as reflected by a higher increase in tumor necrosis factor-alpha (965 +/- 193 vs. 411 +/- 35 pg/mL, p < .0001), whereas the increase of the anti-inflammatory interleukin-10 was not significantly different (95 +/- 15 pg/mL in females vs. 129 +/- 15 pg/mL in males, p = .288). Females exhibited higher baseline levels (9.9 +/- 1.1 vs. 7.0 +/- 0.8 pg/mL in males, p = .042) and an augmented increase in lipopolysaccharide-binding protein, which may explain the more pronounced inflammatory response in females. The lipopolysaccharide-induced change in heart rate was not significantly different between the genders, whereas blood pressure decreased more in females (p < .0001). Lipopolysaccharide administration significantly attenuated the norepinephrine sensitivity in males (p = .002), whereas no lipopolysaccharide-induced effect was observed in females (p = .552; difference between groups, p = .045). During experimental human endotoxemia, females showed a more pronounced proinflammatory innate immune response associated with less attenuation of norepinephrine sensitivity. These findings may be relevant in view of the profound and incompletely explained differences in incidence and outcome of sepsis among male and female patients.

Markers of muscle ischemia, necrosis, and inflammation following uterine artery embolization in the treatment of symptomatic uterine fibroids

The objective of the study was to quantify markers of myometrial ischemia, necrosis, and inflammation in women undergoing uterine artery embolization (UAE). Women with symptomatic fibroids were randomized to treatment with UAE (n = 14) or abdominal myomectomy (n = 11). Peripheral venous blood samples were taken before and after the procedure, at 24 hours and 6 weeks. Creatine kinase (CK) and ischemia-modified albumin (IMA) were measured as markers of necrosis and ischemia. Inflammation was assessed by measurement of C-reactive protein (CRP). Changes in the markers following UAE and myomectomy were measured. Following UAE, no change was seen in CK or IMA, but CRP was raised only at 6 weeks. At 24 hours after myomectomy, there were significant rises in all 3 markers, with a return to normal by 6 weeks. No significant ischemia or necrosis occurs in the myometrium following UAE, whereas the delayed rise in CRP is likely to reflect necrosis in fibroids.

High estrogenic impact on the liver by transdermal contraceptive patch

Evaluation of: White T, Ozel B, Jain JK, Stanczyk FZ. Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins. Contraception 74, 293–296 (2006).In a randomized trial, the effects on sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), thyroxin-binding globulin (TBG) and C-reactive protein (CRP) of three cycles of treatment with a contraceptive patch containing ethinylestradiol (EE) and norelgestromin versus treatment with an oral contraceptive (OC) containing EE and norgestimate were compared. There was a significantly higher increase in the levels of SHBG and TBG during treatment with the patch than with the OC, whereas the estrogen-induced rise in CBG and CRP was similar. The results suggest a higher impact on estrogen-sensitive hepatic proteins of the contraceptive patch than of an OC due to the higher exposure of the women to EE. It has been reported that the relative risk of venous thromboembolism increases during treatment with the transdermal con...

Influence of Genetic Variation in the C‐Reactive Protein Gene on the Inflammatory Response During and After Acute Coronary Ischemia

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene (CRP) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, -757T > C and -286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP -286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.

Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response.

The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs). The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase. In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured. A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.

Effects of dydrogesterone and norethisterone, in combination with oestradiol, on lipoproteins and inflammatory markers in postmenopausal women

Objective The lack of cardiovascular benefit from postmenopausal hormone replacement therapy (HRT) in randomised controlled trials is not readily explained. The androgenic properties of progestogens could be crucial in understanding the results of these studies, all of which employed medroxyprogesterone. We have previously reported that medroxyprogesterone has some androgenic effects intermediate between those of the more androgenic norethisterone and the less androgenic desogestrel. To examine the androgenicity of progestogens further, we compared the effects of dydrogesterone (DGT) that is even less androgenic than desogestrel, and norethisterone (NET), on lipoproteins and inflammatory markers while maintaining the same oestrogen dose. Method In a crossover trial, 25 non-hysterectomised postmenopausal women were randomised to two preparations of HRT each for three 28-day treatment cycles. Both HRT regimens comprised oestradiol (1 mg). One also included DGT (10 mg) and the other NET (1 mg). Oestradiol was taken continuously and the progestogens sequentially. Measurements were made at baseline and on the last day of the oestradiol phase and the last day of the progestogen phase in the third treatment cycle of each regimen. Results NET was more effective than DGT in significantly reducing lipoprotein (a) ( p < 0.05). NET was, however, associated with significantly lower levels of high-density lipoprotein (HDL) cholesterol ( p = 0.001) and triglycerides ( p < 0.05). NET was less effective in opposing the oestrogen-related increase in C-reactive protein (CRP). Interleukin-6 levels did not change with either progestogen. Conclusion The effect of androgenic progestogens on cardiovascular risk factors may not be as deleterious as previously assumed, especially if the lower HDL levels result from more efficient reverse cholesterol transport. The hormone related rise in C-reactive protein , without a corresponding increase in interleukin-6, may not represent a systemic inflammatory response.

Comparison of surgical stress between laparoscopic and open appendectomy in children

Purpose The present study aimed to evaluate laparoscopic appendectomy (LA) in comparison with conventional open appendectomy (OA) in children, with special emphasis on the extent of surgical trauma after LA and OA, and to assess whether LA had any clear advantages compared with conventional OA. Methods A total of 160 patients with a median age of 7.9 years (range 3-15 years) were studied. Sixty-nine of them underwent LA, and the remaining 91 underwent OA. Serum interleukin (IL) 6 and C-reactive protein (CRP) levels which are thought to play a pivotal role in the pathogenesis of surgical trauma and can also be used to monitor the magnitude of surgical trauma were measured using an enzyme-linked immunosorbent assay before surgery and 12 hours after surgery. In addition, we compared operating time, hospital stay, incidence of wound infection, and incidence of intra-abdominal infection. Results The operative time of normal and suppurative appendix in the laparoscopic group was significantly shorter than that in the open group, respectively, but the operative time of gangrenous appendix was not different between the laparoscopic group and open group. The hospital stay in the laparoscopic group was also significantly shorter than that in the open group. Postoperatively, 1 patient had port-site infection in the laparoscopic group, whereas 10 had wound infection in the open group; this difference was highly significant ( χ 2 = 4.19, P < .05). Three patients in the open group and 2 patients in the laparoscopic group had intra-abdominal infection, and the difference had no statistically significant difference ( χ 2 = 0.10, P < .05). Preoperative IL-6 levels were not different between the 2 groups, but the rise (preoperative vs postoperative) of IL-6 in the laparoscopic group was remarkably less than that in the open group. Similar results were obtained for CRP; serum CRP levels in the basal state were not different between the 2 groups, but the rise (preoperative vs postoperative) of CRP in the laparoscopic group was also substantially less compared with that in the open group. Conclusions LA for children was as safe and effective as the open procedure and had significant advantages over OA because of less operating time, less postoperative complications, less surgical trauma, and more rapid postoperative recovery.

Diabetes, Coronary Intervention, and Platelet Glycoprotein IIb/IIIa Blockade

Diabetes mellitus is associated with inferior outcome after percutaneous coronary intervention (PCI).1 Platelet glycoprotein IIb/IIIa (GP IIb/IIIa) inhibition is an important adjunctive therapy during PCI and may be particularly so in patients with diabetes mellitus.2 Platelet GP IIb/IIIa inhibitors are potent antithrombotic agents, and in several large-scale clinical trials with balloon angioplasty and coronary stenting, these agents have produced a consistent and marked reduction in both 30-day ischemic events and long-term (up to 1 to 3 years) mortality.3 In most cases, a greater magnitude of survival benefit with abciximab has been observed in patients with diabetes as compared with patients without diabetes.3–5 Furthermore, clinical risk stratification with diabetes and other variables reliably predicts abciximab benefit for late survival, thereby validating the important mortality benefits (nearly 3 lives saved per 100 patients treated) with abciximab use in high-risk patients during PCI.6 This large body of evidence has led to the widespread acceptance of platelet GP IIb/IIIa inhibitors to neutralize the excessive mortality associated with PCI among patients with diabetes as compared with patients without diabetes. See p 3627 The introduction of clopidogrel has changed the landscape of clinical outcomes in PCI. In patients with diabetes, clopidogrel has been shown to be superior to aspirin in reducing recurrent ischemic events.7 The use of preprocedural clopidogrel can attenuate the increase in C-reactive protein and other inflammatory markers after PCI, even in the presence of abciximab.8,9 Pretreatment with clopidogrel (300 to 600 mg) has been suggested to reduce ischemic events during PCI, and long-term (1 year) clopidogrel therapy has been shown to reduce long-term clinical events.10 Recently, the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment) study found no benefit with abciximab therapy versus placebo in low- and intermediate-risk patients undergoing PCI who …

Less systemic cytokine response in patients following microendoscopic versus open lumbar discectomy

The magnitude of the tissue damage from surgery impacts the trauma response. This response is proportional to the severity of surgical stress. Systemic cytokines are recognized as markers of postoperative tissue trauma. Microendoscopic discectomy (MED) recently has become popular for treating lumbar disc herniations, and is associated with favorable clinical outcomes compared with open discectomy (OD). This study postulates that MED is a less traumatic procedure, and therefore has a lower surgical stress response compared to OD. In this study, a quantitative comparison of the overall effects of surgical trauma resulting from MED and OD was performed through analyzing patient systemic cytokines response. From April, 2002 to June, 2003, 22 consecutive patients who had symptomatic lumbar disc herniations were prospectively randomized to undergo either intracanalicular MED ( N = 10) or OD ( N = 12). In this study, the Vertebroscope System (Zeppelin, Pullach, Germany) was used to perform the endoscopic discectomy procedure in all MED patients. Serum levels of tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) were measured before surgery and at 1, 2, 4, 8 and 24 h after surgery using an enzyme-linked immunosorbent assay. Serum C-reactive protein (CRP) was measured at the same time interval. The results showed the MED patients had shorter postoperative hospital stay (mean, 3.57 ± 0.98 vs. 5.92 ± 2.39 days, p = 0.025) and less intraoperative blood loss (mean, 87.5 ± 69.4 vs. 190 ± 115 ml, p = 0.042). The operating length, including the set-up time, was longer in the MED group (mean, 109 ± 35.9 vs. 72.1 ± 17.8 min, p = 0.01). The mean size of skin incision made for the MED patients was 1.86 ± 0.13 cm (range 1.7–2.0 cm); and 6.3 ± 0.98 cm for the OD patients (range 5.5–8 cm), p = 0.001. The patients’ pain severity of the involved limbs on 10-point Visual Analog Scale before operation in MED group was 7.5 ± 0.3 (range 6–9) and 8 ± 0.2 (range 7–9) in OD group, p = 0.17; and after surgery, 1.5 ± 0.2 (range 1–2) in MED group and 1.4 ± 0.1 (range 1–3) in OD group, p = 0.91. CRP levels peaked at 24 h in both groups, and OD patients displayed a significantly greater postoperative rise in serum CRP (mean, 27.78 ± 15.02 vs. 13.84 ± 6.25 mg/l, p = 0.026). Concentrations of TNF-α, IL-1β, and IL-8 were detected only sporadically. Serum IL-6 increased less significantly following MED than after OD. In the MED group, IL-6 level peaked 8 h after surgery, with the response statistically less than in the open group (mean, 6.27 ± 5.96 vs. 17.18 ± 11.60 pg/ml, p = 0.025). A statistically significant correlation was identified between IL-6 and CRP values ( r = 0.79). Using the modified MacNab criteria, the clinical outcomes were 90% satisfactory (9/10) in MED patients and 91.6% satisfactory (11/12) in OD patients at a mean 18.9 months (range 10–25) follow-up. Based on the current data, surgical trauma, as reflected by systemic IL-6 and CRP response, was significantly less following MED than following OD. The difference in the systemic cytokine response may support that the MED procedure is less traumatic. Moreover, our MED patients had achieved satisfactory clinical outcomes as the OD patients at a mean 18.9 months follow-up after surgery.

Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention

This study sought to determine the effect of clopidogrel pretreatment on the increase in C-reactive protein (CRP) after percutaneous coronary intervention. Clopidogrel pretreatment attenuated the periprocedural increase in CRP by 65% and was independently associated with an attenuation in the CRP increase in a multivariate model.

Systemic complement activation following human acute ischaemic stroke.

The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia-reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C-reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow-up period of 12 months. Nine healthy gender- and age-matched subjects served as controls. The terminal SC5b-9 complement complex (TCC), CRP, soluble adhesion molecules (L-, E- and P- selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0.54 to 0.74 AU/ml at 72 h (P = 0.032), reached maximum at 7 days (0.90 AU/ml, P < 0.001), was still significantly increased at 12 days (0.70 AU/ml, P = 0.009) and thereafter normalized. CRP increased significantly from 1.02 to 2.11 mg/l at 24 h (P = 0.023), remained significantly increased for 1 week (2.53-2.94 mg/l, P = 0.012-0.017) and thereafter normalized. TCC and C-reactive protein (CRP) correlated significantly (r = 0.36, P < 0.001). The increase in TCC and CRP correlated to the size of infarction (r = 0.80 and P = 0.017 for TCC; r = 0.72 and P = 0.043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.

Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia

A patient was admitted for fever and acute respiratory failure (ARF), rapidly progressive tetraparesis, delirium, behavioral abnormalities, and diplopia. Leukocytosis and a rise in C-reactive protein were present. A syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was also diagnosed. Lumbar puncture yielded colorless CFS with mononuclear pleocytosis and protein rise. Electrodiagnosis revealed demyelinating polyneuropathy and axonal degeneration. Serum IgG and IgM for mycoplasma pneumoniae (MP) was consistent with acute infection, and erythromycin was started with rapid resolution of symptoms. Contrarily to most reports, an associated respiratory disease was not present and SIADH in association with MP has been reported only once, in a patient without direct central nervous system (CNS) involvement. Differential diagnosis and possible pathogenic mechanisms are discussed.

C-Reactive Protein Response Following Pediatric Orthopaedic Surgery

The purpose of this study was to describe the pediatric C-reactive protein (CRP) response following orthopaedic surgery, specifically addressing whether CRP values in children return to normal within 3 weeks as they do in adults. Children undergoing elective orthopaedic procedures had serum CRP values measured before surgery and then on days 3, 7, and 21 after surgery. These intervals were chosen to assess the rise, fall, and return to normal of CRP levels. Twenty-two children were studied. CRP levels on day 3 varied from normal to 22.2 mg/dL (mean 7.3 mg/dL), on day 7 they averaged 2.2 mg/dL, and at 3 weeks all values were normal. None of the patients had postoperative infections. The authors concluded that the CRP rise in children may be more varied than in adults. In children, CRP levels return to normal within 3 weeks after surgery. This information can be useful in identifying postoperative infections in children.