Outcomes comparison of 5 coated cardiopulmonary bypass circuits versus an uncoated control group of patients undergoing cardiac surgery.

UNLABELLED: Attenuated inflammatory response and decreased platelet activation have been claimed repeatedly when biocompatible circuits are used for cardiopulmonary bypass. We evaluated five Health Canada approved biocompatible circuit coatings (BCC) against an un-coated control group to determine their effectiveness in improving post-operative outcomes. Patients were assigned to the Control group or one of the 5 coated circuit groups: 40 Control; 33 Trillium; 32 Phisio; 34 Bioline; 33 X; and 11 GBS. Measured outcomes included: ventilator time; ICU time; post-operative chest tube drainage and transfusion volume; high sensitivity C-reactive protein (hsCRP); tau protein; and pre- and 72-hour post-operative anti-saccadic eye movement test comparisons. RESULTS: 183 patients were enlisted into the study. One arm of the study (GBS) was abandoned after 11 patients on account of inconsistent pressure excursions within the oxygenator and the excessive consumption of platelets necessitating transfusion. Patients in the X-coated group had significantly longer ventilator and intensive care unit (ICU) time compared to the three remaining coated circuit study groups. Though not significant, patients in the X group also demonstrated the highest post-operative chest tube losses, the most platelet transfusions, the highest tau protein levels and the lowest post-operative anti-saccadic eye movement test (ASEMT) results compared to the three remaining coated groups. The patients in the Trillium, Bioline and Phisio groups showed an improvement in ventilator and ICU time relative to the Control group. The diabetic patients in the Trillium, Bioline and Phisio groups showed an improvement in bleeding relative to the diabetic patients in the Control group. CONCLUSION: We compared all 5 coated circuits approved for clinical use in Canada against an uncoated control circuit. Three of the 5 coated circuits (Trillium, Phisio and Bioline BCC) were found to improve ventilator and ICU time compared to Control. Further studies are indicated to validate these results and their impact upon approval criteria, purchasing choices and safe clinical practice, especially as applied to higher risk diabetic patients.

The impact of different biocompatible coated cardiopulmonary bypass circuits on inflammatory response and oxidative stress.

This study was to compare the impact of different biocompatible coated circuits on inflammatory response and oxidative stress induced during cardiopulmonary bypass (CPB). Seventy-eight patients undergoing elective coronary artery bypass grafting (CABG) with CPB were randomly assigned to five groups with different biocompatible coated circuits: Trillium, Bioline, Phosphorylcholine, Polymethoxyethyl acrylate (PMEA), and the uncoated control group. Blood was drawn at three different time points: before CPB, 6 and 72 hours post CPB. Unlike the Trillium group, serum levels of TNF-alpha in the Bioline and Phosphorylcholine groups significantly increased only at 72 hours post CPB (p < 0.05). Serum levels of IL-6 significantly increased at 6 and 72 hours post CPB in all groups (p < 0.01). The Trillium group showed a significant increase of IL-10 compared to the control group at 72 hours post CPB (p < 0.05). Serum levels of NOx in the Phosphorylcholine group significantly decreased at 6 hours post CPB compared to baseline (p < 0.05). Both the Bioline and Phosphorylcholine groups showed statistical decreases in serum NOx levels compared with other groups at 6 hours post CPB (p < 0.05). A significant difference in NOx levels between the Bioline and the control group was also observed at 72 hours post CPB. Myeloperoxidase levels were significantly elevated at 6 and 72 hours post CPB in all groups (p < 0.05). Inflammatory response and oxidative stress are elevated during CABG with CPB. Heparin-coated and the Phosphorylcholine-coated circuits induce less inflammatory responses and oxidative stress compared to other circuits.

Neuroprotective and neurotrophic effects of quinic acids from Aster scaber in PC12 cells.

Aster scaber T. (Asteraceae) has been used to treat bruises, snakebite, headache, and dizziness in traditional Chinese medicine. In the present study, the neuroprotective effect of four quinic acid derivatives from A. scaber on amyloid Abeta-induced PC12 cell toxicity was investigated. When cells were treated with quinic acid derivatives prior to Abeta, cell toxicity was significantly diminished. Among quinic acid derivatives, (-)4,5-dicaffeoyl quinic acid (1) gave the highest protection against Abeta-induced cell toxicity. In addition, the neurotrophic effects of compounds were evaluated by microscopically monitoring their potency to induce neurite outgrowth in PC12 cells. Four quinic acid derivatives from A. scaber promoted neurite outgrowth in PC12 cells. Interestingly, a novel quinic acid, (-)3,5-dicaffeoyl-muco-quinic acid (2) was more effective than the other compounds in promoting neurite outgrowth. Unlike nerve growth factor, the withdrawal of quinic acids did not result in any significant decrease in cell viability. The results suggest that quinic acid derivatives from A. scaber might potentially be used as a therapeutic agent in Alzheimer disease.

Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways.

Oxidative stress plays a critical role in cardiac injuries during ischemia/reperfusion. Insulin-like growth factor-1 (IGF-1) promotes cell survival in a number of cell types, but the effect of IGF-1 on the oxidative stress has not been elucidated in cardiac muscle cells. Therefore, we examined the role of IGF-1 signaling pathway in cell survival against H2O2-induced apoptosis in H9c2 cardiac myoblasts. H2O2 treatment induced apoptosis in H9c2 cells, and pretreatment of cells with IGF-1 suppressed apoptotic cell death. The antiapoptotic effect of IGF-1 was blocked by LY294002 (an inhibitor of phosphatidylinositol 3-kinase) and by PD98059 (an inhibitor of extracellular signal-regulated kinase (ERK)). The protective effect of IGF-1 was also blocked by rapamycin (an inhibitor of p70 S6 kinase). Furthermore, H9c2 cells stably transfected with constitutively active PI 3-kinase (H9c2-p110*) and Akt (H9c2-Gag-Akt) constructs were more resistant to H2O2 cytotoxicity than control cells. Although H2O2 activates both p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), IGF-1 inhibited only JNK activation. Activated PI 3-kinase (H9c2-p110*) and pretreatment of cells with IGF-1 down-regulated Bax protein levels compared to control cells. Taken together, our results suggest that IGF-1 transmits a survival signal against oxidative stress-induced apoptosis in H9c2 cells via PI 3-kinase and ERK-dependent pathways and the protective effect of IGF-1 is associated with the inhibition of JNK activation and Bax expression.

Transanal hemorrhoidal dearterialization is an alternative to operative hemorrhoidectomy.

BACKGROUND: Transanal hemorrhoidal dearterialization (THD), a new approach for patients who would otherwise require an operative hemorrhoidectomy, accomplishes hemorrhoidal symptom relief with far less postoperative pain than an operative hemorrhoidectomy. METHODS: THD, an ambulatory procedure, employs a specially designed proctoscope coupled with a Doppler transducer to allow identification and suture ligation of the hemorrhoidal arteries. RESULTS: Sixty patients between ages 22 and 87 were treated. Bleeding was fully corrected in 88%, protrusion in 92%, and pain in 71%. Two patients (3%) failed to improve with THD. Complications included pain resulting in greater than 2 days loss of work in 5 patients, postoperative perirectal thromboses developed in 4 patients, and an anal fissure developed in 1 patient. CONCLUSIONS: THD was an effective alternative to operative hemorrhoidectomy. It may be the only option for patients where an operative hemorrhoidectomy is contraindicated because of incontinence.

Anorectal Crohn's disease: surgical and medical management.

In some patients with Crohn's disease the anorectal complications are the major cause of symptoms and morbidity. Anorectal Crohn's disease may be present in patients with intestinal Crohn's disease, may be the initial manifestation of the disease, or rarely occurs without involvement of Crohn's disease elsewhere in the intestinal tract. The pathogenesis of these anorectal complications remains to be clarified. The anorectal examination is very important in the assessment of patients with suspected or documented inflammatory bowel disease. Meticulous physical examination, examination under anaesthesia and radiological imaging modalities may be utilised to specifically identify the location of abscesses and fistulae. Treatment strategy should be directed toward symptomatic relief; the most important symptom is pain. In most patients this pain will be attributable to an incompletely drained rectal abscess. Simple incision and drainage procedures are often all that is required as initial treatment of anorectal abscesses. Treatment of the anorectal fistulae that occur secondary to Crohn's disease requires combined medical and surgical therapy. Drug therapy is more often initiated for Crohn's disease that involves other areas of the gastrointestinal tract. The anorectal manifestations often respond to these same medications. Lay-open procedures (fistulotomies) are often all that is required surgically for simple (low) anorectal fistulae. High (complex) fistulae that involve large portions of the anorectal muscular ring are more difficult to treat. Patients with these fistulae must be treated on an individual basis, usually local surgical therapy combined with a medical regimen. Many surgical procedures are performed and many classes of medications are utilised on patients with these complex anorectal fistulae. Choosing the appropriate surgical and medical interventions is often quite difficult. Although sulfasalazine, mesalazine and corticosteroids have no lasting or maintenance value for fistulae, the immunosuppressive agents mercaptopurine, azathioprine and cyclosporin, the antibacterial metronidazole and the anti-tumour necrosis factor-alpha monoclonal antibody infliximab have varying degrees of effect. The goal of the combined regimen is to cure the fistula, or at least make it minimally symptomatic, without altering the patient's continence.

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation.

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.

Nitric oxide and the cerebral-blood-flow response to somatosensory activation following deafferentation.

The single-vibrissa stimulation model in the rat was utilized to study the microvascular coupling between functional activation and local cerebral blood flow (LCBF) in both normal cortex and in cortex that had been peripherally deafferented. In addition, the role of chronic nitric oxide synthase (NOS) inhibition on the LCBF response to vibrissa stimulation was examined. One-day-old rats underwent deafferentation of all vibrissae on one side of the face, sparing C3, and received daily administration of either saline or N omega-nitro-L-arginine (L-NA). After seven weeks of treatment, LCBF was measured autoradiographically in conscious rats with [14C]N-isopropyl-p-iodoamphetamine while C3 was stimulated bilaterally. Stimulation produced a greater increase in LCBF in the deafferented cortex of both the saline (30.4%) and L-NA treated (25.7%) animals than in the intact cortex (19.9% and 16%, respectively). The area of activation of LCBF (0.176 mm2) was comparable to the area metabolically activated (0.149 mm2), and the increase in area of LCBF activation following deafferentation (169%) was smaller than the increase in area that was metabolically activated (287%). Chronic inhibition of NOS did not alter the spatial extent of the blood-flow response.

Carcinoma arising in anorectal fistulas of Crohn's disease.

PURPOSE: Anorectal fistulas are commonly associated with Crohn's disease. Carcinoma arising in an anal fistula in the absence of Crohn's disease occurs rarely. Carcinoma arising in an anorectal fistula of Crohn's disease is likewise rare and is the subject of this article. METHODS: We have seen eight cases in seven patients. Four of these were squamous carcinoma and three were adenocarcinoma. Details of these seven patients are presented. RESULTS: Two deaths in the four patients with squamous carcinoma and one in the two patients with adenocarcinoma with adequate follow-up suggest a poorer prognosis in both types of malignancy than when these lesions occur without Crohn's disease. CONCLUSION: Carcinoma does arise in the midst of the anorectal fistulas and abscesses of Crohn's disease. Carcinoma arising in a Crohn's disease fistula can be very difficult to diagnose. Examination may be limited by pain, stricture, or induration of the perianal and perineal tissues. Examination under anesthesia can also overlook the lesion. Diagnostic examination under anesthesia yields increases with biopsies or curettage of the fistulous tracts.

Blame and the couples dynamic.

AIDS: Guilt and blame are common in relationships in which one or both parties are HIV-positive; however, counseling may help these people manage their relationships better. One technique used by therapists is Control Mastery Theory, a cognitive, interpersonal, psychoanalytic approach that classifies behavior as either growth-promoting or pathogenic. Control Mastery Theory, designed to break the blame/rage cycle, is based on the theory that a person's beliefs are rooted in their childhood experiences. Therapists use the approach to help clients better understand their responses to their situation and to their partner. A case is presented of an HIV-serodiscordant couple who have years of mutual blaming. The therapist helps the couple explore the pathogenic beliefs underlying their behaviors so that they can gain greater control over their behaviors. To ease transitions during antiviral treatment success, therapists should pay attention to the unconscious, irrational beliefs underlying patient's behaviors.^ieng

Precise anorectal sphincter dilatation--its role in the therapy of anal fissures.

For the past 20 years, internal anal sphincterotomy has generally been considered to be the standard operation for an anal fissure. We sought an alternative form of treatment because of the wound complications inherent in this operation. Anal dilatation, precisely performed with a Parks' retractor opened to 4.8 cm or with a 40-mm rectosigmoid balloon, has been found to cure successfully the fissure in 93 percent and 94 percent, respectively, of each group and to be associated with fewer complications.

Primary anorectal lymphoma. A new manifestation of the acquired immune deficiency syndrome (AIDS).

Non-Hodgkin's lymphomas with particular clinicopathologic features occur with a high incidence in homosexual men affected by AIDS. More frequently than in the general population, these lymphomas have an extranodal location including the gastrointestinal tract. We have recently observed four cases of AIDS-associated lymphomas whose primary location is in the lower rectum and anus. The patients were 27 to 44 years of age, had greatly depressed helper-suppressor T-cell ratios, and antibodies to human immunodeficiency virus (HIV). All four presented with anorectal symptoms and originally had surgery for anorectal fistulas or tumor masses. When staged, three patients had no other organ involvement, the fourth only had lymphoma in an axillary lymph node, and all four had large tumor masses confined within the rectum. In terms of histology, the lymphomas were of undifferentiated or of large cell type and of B-cell phenotype. Lymphomas with primary or major location in the rectum are a rare occurrence in the general population, and until recently, are rare even among the lymphomas associated with the immune deficiency syndrome. At the Lenox Hill Hospital in New York City, no rectal lymphoma among the 58 cases of AIDS-related lymphoma diagnosed during the past 4 years was recorded until 10 months ago. The recognition of the new feature in presentation, a neoplasm associated with AIDS, is obviously important for its early diagnosis and treatment. Its unusual occurrence at the suspected portal of entry of the HIV infection is of interest because it may provide new clues to the association between AIDS and neoplasia.

The fate of the rectal segment after diversion of the fecal stream in Crohn's disease: its implications for surgical management.

Diverting the fecal stream has been considered to benefit the course of Crohn's disease. Clinical signs and symptoms have not, however, been distinguished previously from the objective inflammatory changes in the distal segment. We reviewed the course of 16 consecutive patients with Crohn's disease in whom sigmoidoscopy showed normal mucosa at the time of diversion and who underwent an ileostomy or colostomy, the rectal segment being left in place. As early as 3 months after diversion, all 16 patients showed progressive friability, ulceration, and exudation in the retained rectum. Stricture occurred in four and lead to abdominoperineal resection in three. Four of eight patients with only moderate inflammation on sigmoidoscopy underwent reanastomosis which was followed by a return to a normal-appearing rectal mucosa. The rectal segment inflammed after diversion rarely shows the histological characteristics of Crohn's disease when resected. This leads us to suspect that the disorder of nonspecific "diversion colitis" might account for this phenomenon entirely, or at least it may accelerate the Crohn's disease process. Continuity of the intestinal tract should be maintained in the course of Crohn's disease surgery if feasible. If a diversion is clinically warranted, reanastomosis should be considered as early as possible despite progressive inflammation of the rectal mucosa.

Proctitis after fecal diversion in Crohn's disease and its elimination with reanastomosis: implications for surgical management. Report of four cases.

Diverting the fecal stream has been considered to affect the course of Crohn's disease favorably. Adverse effects on the distal segment have not previously been distinguished from clinical signs and symptoms. The course of four patients with Crohn's disease who underwent fecal diversion with an in situ rectum were observed in whom sigmoidoscopy was initially normal at the time of the diversion, became distinctly abnormal during the year after the diversion, and then returned to normal within 3 mo following reestablishment of intestinal continuity. The entity of nonspecific diversion proctitis might account for this phenomenon independently or by accelerating the Crohn's disease process. The inflammation present was nonspecific and did not show the stigmata of Crohn's disease. Continuity of the intestinal tract should be maintained in the course of Crohn's disease surgery if feasible. If a diversion is clinically warranted, reanastomosis should be considered as early as possible despite evidence of inflammation in the rectal mucosa.

Simplified loop ostomy fixation using rubber tubing.

This technique has simplified ostomy care and has helped reduce skin complications. The ready availability of rubber tubing in the operating room makes this technique quite practical.

Ileostomy prolapse repair utilizing bidirectional myotomy and a meshed split-thickness skin graft.

The correction of an ileostomy prolapse by a modification of the technique of skin-grafted ileostomy as originally introduced by Dragstedt and emphasized by Turnbull and Weakley is reported. The operation is simple, safe, and effective, and provides a new dimension for the correction of a heretofore difficult and frustrating problem. A total of four patients have been similarly managed successfully with no recurrences in 1 to 4 years of follow-up.