Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.

BACKGROUND: Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections. METHODS: Thirteen patients were studied at baseline, 3, 5, and 7 days after discontinuation of clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow(®) assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100(®) (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated-measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100 closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank test was used to compare the frequencies of ≥30%, 11-29%, and ≤10% platelet inhibition between the baseline and subsequent sampling points after discontinuation of clopidogrel. RESULTS: On day 3 after clopidogrel discontinuation, two subjects had ≥30%, seven subjects had 11-29%, and four subjects had ≤10% platelet inhibition; the corresponding numbers were 0, 3, and 10 subjects on day 5 (P=0.04). There were no differences between the ≥30%, 11-29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13 subjects, P=1.0). PFA-ADP closure times were normal throughout the study period except in one patient. CONCLUSIONS: These findings support the recommendation that discontinuation of clopidogrel for 5 days allows >70% of platelet function and might be adequate before a neuraxial injection is performed.

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

BACKGROUND: The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. AIMS: To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. PATIENTS: CD, UC, and normal control subjects were studied. METHODS: The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). RESULTS: Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. CONCLUSIONS: Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Inflammatory bowel disease and pregnancy.

Most women with inflammatory bowel disease who desire to become pregnant can expect to conceive successfully, carry to term, and deliver a healthy infant. However, the management of inflammatory bowel disease during pregnancy remains challenging, and some women with ulcerative colitis or Crohn's disease will have difficulty becoming pregnant or have increased disease symptoms while pregnant. Control of disease activity before conception and during pregnancy is critical to optimize both maternal and fetal health. The natural history of inflammatory bowel disease during pregnancy will be reviewed and the medical and surgical therapy discussed.

New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a pediatric oncology group report of 343 cases.

To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

Adverse reactions to isosulfan blue during selective sentinel lymph node dissection in melanoma.

BACKGROUND: Selective sentinel lymph node (SLN) dissection can spare about 80% of patients with primary melanoma from radical lymph node dissection. This procedure identifies the SLN either visually by injecting isosulfan blue dye around the primary melanoma site or by handheld gamma probe after radiocolloid injection. METHODS: During selective SLN mapping, 1 to 5 ml of isosulfan blue was injected intradermally around the primary melanoma. From November 1993, to August 1998, 406 patients underwent intraoperative lymphatic mapping with the use of both isosulfan blue and radiocolloid injection. Three cases of selective SLN dissection, in which adverse reactions to isosulfan blue occurred, were reviewed. RESULTS: We report three cases of anaphylaxis after intradermal injection with isosulfan blue of 406 patients who underwent intraoperative lymphatic mapping by using the procedure as described above. The three cases we report vary in severity from treatable hypotension with urticaria and erythema to severe cardiovascular collapse with or without bronchospasm or urticaria. CONCLUSIONS: In our series, the incidence of anaphylaxis to isosulfan blue was approximately 1%. Anaphylaxis can be fatal if not recognized and treated rapidly. Operating room personnel who participate in intraoperative lymphatic mapping where isosulfan blue is used must be aware of the potential consequences and be prepared to treat anaphylaxis.

Medical and surgical management of severe colitis.

The management of severe ulcerative colitis and Crohn's colitis remains a challenge, despite significant advances in medical and surgical therapy. Optimal management of the patient with severe colitis requires close collaboration between the gastroenterologist and surgeon. All patients with severe colitis should be hospitalized and treated with intravenous corticosteroids. If significant improvement does not occur within 7 to 10 days, then intravenous cyclosporine therapy or surgery is appropriate. Newer medical therapies, including heparin, tacrolimus, and other immunomodulatory agents, show promise for the treatment of severe colitis. When surgery is necessary, a total abdominal colectomy with ileostomy is the appropriate surgical intervention in most cases. In patients presenting with fulminant colitis, toxic megacolon, or perforation, earlier surgical intervention is indicated. The evaluation of and approach to the medical and surgical management of severe colitis will be reviewed.

Catheter probe assisted endoluminal US in inflammatory bowel disease.

BACKGROUND: Use of an echocolonoscope to examine patients with inflammatory bowel disease is technically difficult. Catheter probe assisted endoluminal ultrasonography (US) may be a feasible alternative. METHODS: Determination of demographic information and clinical disease activity was followed by colonoscopy with biopsy. Catheter probe assisted endoluminal US was performed with measurements of thickness of the intestinal wall and evaluation of the structure of the sonographic layers. RESULTS: Twenty-eight patients, 7 with ulcerative colitis, 11 with Crohn's disease, and 10 healthy control subjects participated in a prospective study. Mean colonic wall thickness was 2.2 +/- 0.1 mm (controls) compared with 4. 1 +/- 0.4 mm (ulcerative colitis) (p < 0.001) and 4.4 +/- 0.4 mm (Crohn's disease) (p < 0.001). Among patients with ulcerative colitis, colonic wall thickness correlated with severity of colonoscopic changes (r = 0.84, p = 0.02). Among patients with Crohn's disease, loss of endosonographic layer structure correlated with disease activity score (r = 0.8, p = 0.003), and colonic wall thickness correlated with the severity of histologic changes (r = 0. 62, p = 0.04). CONCLUSIONS: Catheter probe assisted endoluminal US is technically feasible in the care of patients with inflammatory bowel disease. Endosonographic measurements of colonic wall thickness and layer structure provide clinically significant information.

The influence of human endotoxemia on CD95-induced apoptosis.

BACKGROUND: The responses of monocyte and neutrophil tumor necrosis factor receptor type 1 (TNFR-1) and TNFR-2 during systemic inflammation have been described previously. Several other members of the TNFR superfamily also appear to have regulatory roles in immunocyte function, including apoptosis. However, the response of these other receptor members, such as CD95, to systemic inflammation is unclear. OBJECTIVES: To compare the response of CD95 with that of TNFR during systemic inflammation and to assess the influence of the inflammatory milieu on CD95 function. SETTING: Adult clinical research center of a university hospital. SUBJECTS AND METHODS: Five healthy male subjects were administered intravenous endotoxin (2 ng/kg), and systemic response was measured by cytokine analysis and receptor expression assays during a 48-hour period. CD95 function during systemic inflammation was assessed using a Jurkat cell bioassay for degree of apoptosis. RESULTS: Monocyte and neutrophil CD95 expression exhibited changes parallel to that of TNFR following endotoxin injection. In contrast to soluble TNFR, which was transiently elevated during endotoxemia, soluble CD95 levels remained unchanged from baseline. Jurkat cells incubated in normal and post-endotoxin serum samples equally exhibited less than 10% spontaneous apoptosis. No soluble CD95 ligand was detectable in experimental human endotoxemia. CONCLUSIONS: Cell-associated CD95 exhibited changes parallel to its receptor family member TNFR following endotoxin administration. Soluble CD95 is present in human serum samples, but the levels remained unchanged following endotoxin administration. No soluble CD95 ligand activity was detectable by enzyme-linked immunosorbent assay or by functional assay. The potential protective role of soluble CD95 in human serum samples against CD95 ligand-induced apoptosis remains to be defined.

Sympathetic blockade does not enhance tissue warming during isolated heated limb perfusion.

UNLABELLED: Isolated, heated limb perfusion is used for the treatment of locally recurrent melanoma, intransit metastases, and acral lentiginous melanomas. Tissue warming during this procedure requires adequate perfusion within the isolated extremity. At our institution, spinal or epidural anesthesia was used to produce sympathetic blockade and vasodilation for lower extremity procedures. More recently, we began using mild systemic hyperthermia to produce active thermoregulatory vasodilation. In the presence of heat stress, sympathetic blockade may actually decrease skin blood flow because active cutaneous vasodilation, which is associated with sweating, is dependent on intact sympathetic innervation. We therefore investigated whether the continued use of neuraxial blockade was justified. Twenty patients undergoing lower extremity perfusions were alternately assigned to receive either combined general and spinal anesthesia or general anesthesia alone. All were aggressively warmed using forced air and circulating water. There were no significant differences in tissue temperatures (measured at four sites in the isolated limb) between groups at any time before or after the start of perfusion. Similarly, pump flow (715 +/- 211 mL/min versus 965 +/- 514 mL/min) and the time required to achieve an average tissue temperature of 39 degrees C (43 +/- 16 vs 34 +/- 13 min) were not different between groups (spinal versus no spinal). Sweating was observed in all but three patients at esophageal temperatures of 37.9 +/- 0.6 degrees C. We conclude that sympathetic blockade confers no added benefit for tissue warming during isolated limb perfusions in the presence of induced mild systemic hyperthermia. IMPLICATIONS: Sympathetic blockade prevents adrenergic vasoconstriction, but also inhibits active, neurally mediated cutaneous vasodilation (a normal thermoregulatory response to heat). In slightly hyperthermic patients, we demonstrated that spinal anesthesia does not improve convective tissue warming during isolated, heated limb perfusion. Mild systemic hyperthermia may promote greater vasodilation than sympathetic blockade.

Nausea and vomiting following thyroid and parathyroid surgery.

STUDY OBJECTIVES: To determine the incidence of postoperative nausea and vomiting (PONV) following thyroid and parathyroid surgery. To determine whether PONV is reduced when propofol is used for maintenance of anesthesia as compared to isoflurane and to evaluate the costs and resource consumption associated with these two anesthetic regimens. DESIGN: Randomized, prospective study. SETTING: University-affiliated hospital--a referral center for endocrinologic surgery. PATIENTS: 118 ASA physical status I and II patients, aged 18 years and older, undergoing elective thyroid or parathyroid surgery. INTERVENTIONS: Patients received either isoflurane (0.5 to 1.3% end-tidal) or propofol (50 to 200 micrograms/kg/min) for maintenance of anesthesia. All patients received propofol for induction of anesthesia, succinylcholine or vecuronium, nitrous oxide, and fentanyl. Prophylactic antiemetics were not administered. Postoperative pain was treated with ketorolac, fentanyl, or acetaminophen. MEASUREMENTS AND MAIN RESULTS: Signs and symptoms of nausea and vomiting were graded on a four point scale as 1 = no nausea; 2 = mild nausea; 3 = severe nausea; 4 = retching and/or vomiting. Grades 3 and 4 were grouped together as PONV. The combined incidence of PONV was 54% over the 24-hour postoperative evaluation period. PONV was significantly more common in patients receiving isoflurane than propofol for maintenance of anesthesia (64% vs. 44%). In women (n = 87), the incidence of PONV was significantly greater in those patients who received isoflurane than those who received propofol for maintenance (71% vs. 42%). However, in men (n = 31), there was no significant difference in PONV between anesthetic regimens (47% with isoflurane vs. 50% with propofol). There were no differences in the duration of stay in the postanesthesia care unit, time to discharge from the hospital, or local wound complications (hematomas) between groups. The use of propofol for maintenance of anesthesia was associated with an additional cost, relative to the isoflurane group, of $54.26 per patient. CONCLUSION: Patients undergoing thyroid or parathyroid surgery are at high risk for the development of PONV. Propofol for maintenance of anesthesia, although more expensive than isoflurane, reduces the rate of PONV in women.

Incidence of childhood and adolescent cancer in Texas.

Population-based data from the Texas Cancer Registry were used to describe the incidence of cancer in 1990 among Texas residents younger than 20 years. A total of 788 primary malignant neoplasms were diagnosed. Higher incidence of all cancers was observed among Texas Anglo children compared with Hispanics or African-Americans, and lower rates of central nervous system (CNS) neoplasms were seen among Hispanics. Compared with national data, significantly fewer cases of all cancers combined, non-Hodgkin's lymphoma, neuroblastoma, and CNS neoplasms were seen in Texas Hispanics. The overall incidence of leukemia and acute nonlymphocytic leukemia (ANLL) was highest in Hispanics compared with other Texas children, and a three-fold statistically significant excess of ANLL was evident in Hispanic females compared with national whites. In summary, the incidence of cancer in Texas Hispanic children and adolescents differs from that seen in other racial and ethnic groups. Incidence data for Texas provide additional insight into the descriptive nature of childhood and adolescent cancers.

A double-blind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery.

BACKGROUND AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic agent with similar potency to that of bupivacaine when administered for epidural anesthesia. Ropivacaine, however, may be less cardiotoxic than bupivacaine. Epidural bupivacaine and ropivacaine have been shown to be equally effective in providing sensory block for lower extremity surgery, but they have not been compared for their ability to produce abdominal wall relaxation. METHODS: Sixty-six American Society of Anesthesiologists I-III women, 18-70 years old undergoing elective gynecologic surgery were studied in a randomized, double-blind manner after giving informed consent in an institutionally approved protocol. Thirty-four patients received a single epidural injection of 20 ml 0.75% bupivacaine at the L2-L3-L4 interspace and 32 patients received 20 ml 0.75% ropivacaine in a similar manner. Sensory block was tested with pinprick; motor block with a modified Bromage scale, rectus abdominis muscle (RAM) test and surgeon satisfaction. Statistical analysis was performed using the SigmaStat for Windows computer software. Parametric data were analyzed with Student's t-test, while nonparametric data was analyzed using the Mann-Whitney rank sum test. RESULTS: Results are expressed as mean +/- SD. Times to maximal sensory block and peak sensory level achieved were similar in both groups. However, time to complete sensory regression was significantly longer with bupivacaine than ropivacaine (458 +/- 77 vs. 404 +/- 62 minutes, P < .03). Bupivacaine lower extremity motor block onset was significantly faster than ropivacaine (9 +/- 3 vs. 12 +/- 3 minutes, P < .0013). Time to maximum lower extremity motor block was significantly shorter with bupivacaine than ropivacaine (28 +/- 12 vs. 40 +/- 15 minutes, P < .0234). Duration of lower extremity motor block was significantly longer with bupivacaine than ropivacaine (371 +/- 97 vs. 310 +/- 65 minutes P < .069). There was no significant difference between the two groups for changes in RAM scores or the time to achieve those changes. Maximum motor block scores using the modified Bromage score and surgeon satisfaction with operating conditions also did not demonstrate a significant difference between the two groups. In one instance (with ropivacaine), anesthesia was judged clinically inadequate despite evidence of bilateral epidural anesthesia. CONCLUSIONS: Both 0.75% ropivacaine and 0.75% bupivacaine provide adequate surgical anesthesia for lower abdominal surgery when administered epidurally. However, lower extremity motor block with ropivacaine is significantly shorter and of slower onset and sensory block shorter at these concentrations.

Epstein-Barr virus-associated leiomyosarcomas in liver transplantation recipients. Origin from either donor or recipient tissue.

BACKGROUND: Leiomyosarcoma, a mesenchymal malignancy with smooth muscle differentiation, is extremely rare in children. Immunosuppression, due to either antirejection medication in organ transplantation recipients or human immunodeficiency virus infection (HIV), appears to constitute a predisposition. METHODS: Two cases of leiomyosarcoma in pediatric liver transplantation recipients were investigated and compared clinically with respect to site of origin and course of the disease and pathologically by routine histology and electron microscopy, by forensic DNA methodology for origin from donor or recipient tissue, and by EBER-1 in situ hybridization for evidence of latent Epstein-Barr virus (EBV) infection. RESULTS: A 9-year-old male developed a high grade, poorly differentiated leiomyosarcoma in his allografted liver 2 years after transplantation, and despite antineoplastic chemotherapy, he died of metastatic disease. The genotype of his tumor indicated an origin from allografted tissue. A 12-year-old female had a low grade retroperitoneal leiomyosarcoma involving the superior mesenteric vein. After resection, she remained disease free without chemotherapy. The genotype of her tumor indicated an origin from native tissue. In both tumors, latent EBV infection was documented. CONCLUSIONS: Neoplastic smooth muscle proliferation in immunosuppressed liver transplantation recipients is analogous to the more common posttransplantation lymphoproliferative disorder in involving transformation of either engrafted donor tissue or recipient tissue elsewhere in the body, in displaying a wide spectrum of histologic differentiation, grade and clinical behavior, and in exhibiting evidence of latent EBV infection.

Safety and cost effectiveness of early hospital discharge of lower risk children with cancer admitted for fever and neutropenia.

BACKGROUND: Standard treatment for fever during periods of chemotherapy-induced neutropenia includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. This study prospectively evaluates the safety and cost-effectiveness of early discharge of selected low risk children before recovery from neutropenia. METHODS: We studied 74 children with cancer during 131 consecutive admissions for fever during a period of neutropenia. All patients initially were hospitalized and received broad-spectrum antibiotics. Intravenous antibiotic therapy was discontinued, and the patients promptly were discharged even if they had an absolute neutrophil count (ANC) of less than 500 cells/mm3 as long as they were afebrile, appeared clinically well, had negative cultures, exhibited control of local infection, and showed hematologic evidence of bone marrow recovery. RESULTS: Intravenous antibiotics were discontinued in 82 cases (63%) before recovery of the ANC to more than 500 cells/mm3, and 78 patients were discharged immediately. None of 70 patients discharged while neutropenic but exhibiting a rising ANC at the time of discharge developed recurrent fever and required readmission. Thirty of these children had an improving localized infection when intravenous antibiotics were discontinued and completed a course of oral antibiotics at home. The estimated mean savings in hospital charges due to early discharge was $5058 per patient. CONCLUSIONS: Low risk children with cancer who are hospitalized and treated for fever and neutropenia but appear clinically well may have intravenous antibiotics discontinued and be discharged safely irrespective of the ANC, as long as their granulocyte count is rising. This approach shortens hospital stays and results in considerable cost savings.

Final attained height in patients successfully treated for childhood acute lymphoblastic leukemia.

We evaluated final adult height in 109 patients treated for childhood acute lymphoblastic leukemia on two multiarm Pediatric Oncology Group protocols between 1974 and 1981. Fifty-one patients received 2400 cGy cranial irradiation (XRT), and 58 patients received no XRT. All patients had no central nervous system involvement at diagnosis, achieved and maintained a complete response, entered puberty spontaneously, and had achieved final height. Height data were converted to standardized deviation scores. Mean age at diagnosis was 7.8 +/- 4.2 years. Distribution of heights at diagnosis was similar to that of the U.S. population. Relative to gender-specific heights for the population, female subjects in this study had lower attained heights than male subjects (p = 0.03). There was a monotonic trend of patients treated at an earlier age to have a reduction in final height (p = 0.057). Cranial irradiation was strongly associated with final height (mean standardized deviation score with XRT = -1.04 and without XRT = -0.14; p < 0.001). Final height was not associated with age at diagnosis, prognostic risk group, or Pediatric Oncology Group protocol. By multivariate analysis, only XRT and XRT x age were significantly associated with final height (p < 0.001 and p = 0.002, respectively). There was no significant gender effect. We conclude that XRT is significantly associated with reduced final adult height after treatment for childhood acute lymphoblastic leukemia. For survivors, therapy devoid of XRT does not appear to affect final height.