Calcitonin precursors in the prediction of severity of acute pancreatitis on the day of admission

BACKGROUND: Calcitonin precursors are sensitive markers of inflammation and infection. The aim of this study was to evaluate the role of plasma calcitonin precursor levels on the day of admission in the prediction of severity of acute pancreatitis, and to compare this with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. METHODS: Plasma concentrations of calcitonin precursors were determined on admission in 69 patients with acute pancreatitis. APACHE II scores were calculated on admission. Attacks were classified as mild (n = 55) or severe (n = 14) according to the Atlanta criteria. Plasma calcitonin precursor levels were determined with a sensitive radioimmunoassay. RESULTS: On the day of hospital admission, plasma levels of calcitonin precursors were significantly greater in patients with a severe attack compared with levels in those with a mild attack of pancreatitis (median 64 versus 25 fmol/ml; P = 0.014), but the APACHE II scores were no different (median 9 versus 8; P = 0.2). The sensitivity, specificity, positive predictive and negative predictive values, and accuracy for the prediction of severe acute pancreatitis were 67, 89, 57, 93 and 85 per cent respectively for plasma calcitonin precursor levels higher than 48 fmol/ml, and 69, 45, 23, 86 and 50 per cent respectively for an APACHE II score greater than 7. Differences in the specificity and accuracy of the two prognostic indicators were significant (P < 0.001 and P = 0.001 respectively). A plasma calcitonin precursor concentration of more than 160 fmol/ml on admission was highly accurate (94 per cent) in predicting the development of septic complications and death. CONCLUSION: The assay of plasma calcitonin precursors on the day of admission to hospital has the potential to provide a more accurate prediction of the severity of acute pancreatitis than the APACHE II scoring system.     

Clinical experience with mixed chimerism to induce transplantation tolerance

Lymphohematopoietic chimerism was first shown to be associated with donor‐specific allograft tolerance more than 60 years ago. However, early clinical experience with bone marrow transplantation soon revealed that conventional, myeloablative approaches were far too toxic and the risk of graft‐versus‐host disease too great to justify using this technology for the purpose of organ allograft tolerance induction in the absence of malignant disease. In this review, we discuss a step‐wise approach that has been applied by several centers to establish less toxic approaches to using hematopoietic cell transplantation (HCT) for tolerance induction. These steps include (i) feasibility and efficacy data for tolerance induction in large animal models; (ii) safety data in clinical trials for patients with hematologic malignancies; and (iii) pilot trials of combined HCT and kidney transplantation for tolerance induction. Thus far, only one published trial conducted at the Massachusetts General Hospital in Boston has achieved long‐term acceptance of human leukocyte antigen‐mismatched kidney allografts without chronic immunosuppressive therapy. Alternative protocols have been successful in large animals, but long‐term organ allograft tolerance has not been reported in patients. Thus, proof‐of‐principle that nonmyeloablative induction of mixed chimerism can be used intentionally to induce organ allograft tolerance has now been achieved. Directions for further research to make this approach applicable for a broader patient population are discussed.     

Posttraumatic stress symptoms, PTSD, and risk factors among lower Manhattan residents 2-3 years after the September 11, 2001 terrorist attacks

Manhattan residents living near the World Trade Center may have been particularly vulnerable to posttraumatic stress disorder (PTSD) after the September 11, 2001 (9/11) terrorist attacks. In 2003-2004, the authors administered the PTSD Checklist to 11,037 adults who lived south of Canal Street in New York City on 9/11. The prevalence of probable PTSD was 12.6% and associated with older age, female gender, Hispanic ethnicity, low education and income, and divorce. Injury, witnessing horror, and dust cloud exposure on 9/11 increased risk for chronic PTSD. Postdisaster risk factors included evacuation and rescue and recovery work. The results indicate that PTSD is a continued health problem in the local community. The relationship between socioeconomic status and PTSD suggests services must target marginalized populations. Followup is necessary on the course and long-term consequences of PTSD.     

High flow priapism due to an arterial-lacunar fistula complicating initial veno-occlusive priapism

High flow or arterial priapism is rare, caused by unregulated arterial blood flow from a lacerated cavernous artery or branch entering directly into lacunar spaces, bypassing the protective, high resistance helicine arterioles and resulting in an arterial-lacunar fistula (ALF) and usually occurs following direct blunt or penetrating perineal trauma. Clinical features include delayed onset of a constant, painless, nontender erection of incomplete rigidity with potential for full rigidity with sexual stimulation. Colour duplex Doppler ultrasonography (CDU) is reliable in the diagnosis of arterial priapism. Treatment by arterial ligation, super-selective embolisation with autologous clot, gelatin sponge or microcoil, duplex guided compression, systemic or intracavernous administration of a variety of alpha-adrenergic agents or methylene blue, mechanical compression/ice packs or expectant management has been reported.     

Laparoscopic antireflux surgery in the lung transplant population

BACKGROUND: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. METHODS: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. RESULTS: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). CONCLUSIONS: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery.     

Gender differences in patellofemoral joint biomechanics

Patellofemoral pain is associated with patellar malalignment and quadriceps weakness which are seen more commonly in women. The objective of the current study was to determine the effects of gender, vastus medialis strength, and tibial rotation on patellofemoral joint biomechanics. Twelve fresh-frozen knees from cadavers were tested using a custom knee jig. Anatomic multiplane loading of the extensor mechanism was used with varying vastus medialis loads. Patellofemoral contact area and pressure were measured using pressure sensitive film at knee flexion angles of 0 degrees, 30 degrees, 60 degrees, and 90 degrees with the tibia in neutral and 15 degrees internal and external tibial rotation. Patellofemoral joint contact areas in specimens from men were larger at knee flexion angles greater than 30 degrees. A significant increase in mean patellofemoral contact pressures was seen for specimens from women when compared with specimens from men at 0 degrees and 30 degrees knee flexion. The knees from women also showed a greater change in contact pressures to varying vastus medialis load at knee flexion angles of 0 degrees, 30 degrees, and 60 degrees. The results of the current study indicate that there are gender differences in patellofemoral contact areas and pressures. These differences may help explain the increased incidence of patellofemoral disorders in women.     

Laparoscopic appendectomy is superior to open appendectomy in obese patients

BACKGROUND: There are minimal data comparing laparoscopic appendectomy (LA) with open appendectomy (OA) in obese patients. METHODS: We reviewed consecutive adult patients from 2003 to 2005 who underwent an appendectomy at a University-affiliated teaching hospital. Obesity was defined as a body mass index of 30 or greater. Outcome measures included length of stay, surgical times, intra-abdominal abscesses, wound infections, and hospital charges. RESULTS: There were 116 patients with a mean body mass index of 35. Eighty-five patients underwent LA, 12 were converted to open, 4 of 12 (31%) were perforated. Thirty-one patients underwent OA. Overall, 21 (18%) were perforated. Length of stay for LA was better, 3.4 days versus 5.5 days for OA (P = .02), and wound closure rate was better, 90% for LA versus 68% for OA (P < .01). Other outcome measures were equivalent. CONCLUSIONS: LA is associated with shorter lengths of stay, fewer open wounds, and equivalent hospital charges and intra-abdominal abscess rates; and should be considered the procedure of choice for obese patients with appendicitis.     

Family-centered Preparation for Surgery Improves Perioperative Outcomes in Children: A Randomized Controlled Trial

Background: Children and parents experience significant anxiety and distress during the preoperative period. Currently available interventions are having limited efficacy. Based on an integration of the literature in both the anesthesia and psychological milieus, the authors developed a behaviorally oriented perioperative preparation program for children undergoing surgery that targets the family as a whole.

Methods: Children and their parents (n = 408) were randomly assigned to one of four groups: (1) control: received standard of care; (2) parental presence: received standard parental presence during induction of anesthesia; (3) ADVANCE: received family-centered behavioral preparation; and (4) oral midazolam. The authors assessed the effect of group assignment on preoperative anxiety levels and postoperative outcomes such as analgesic consumption and emergence delirium.

Results: Parents and children in the ADVANCE group exhibited significantly lower anxiety in the holding area as compared with all three other groups (34.4 +/- 16 vs. 39.7 +/- 15; P = 0.007) and were less anxious during induction of anesthesia as compared with the control and parental presence groups (44.9 +/- 22 vs. 51.6 +/- 25 and 53.6 +/- 25, respectively; P = 0.006). Anxiety and compliance during induction of anesthesia was similar for children in both the ADVANCE and midazolam groups (44.9 +/- 22 vs. 42.9 +/- 24; P = 0.904). Children in the ADVANCE group exhibited a lower incidence of emergence delirium after surgery (P = 0.038), required significantly less analgesia in the recovery room (P = 0.016), and were discharged from the recovery room earlier (P = 0.04) as compared with children in the three other groups.     

Suberoyl Bishydroxamic Acid Inhibits Cellular Proliferation by Inducing Cell Cycle Arrest in Carcinoid Cancer Cells

Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative treatments are needed. In this study, we characterized the effects of suberoyl bishydroxamic acid (SBHA), a histone deacetylase inhibitor, on the growth and neuroendocrine phenotype of carcinoid cancer cells. SBHA treatment of human gastrointestinal and pulmonary carcinoid cancer cells resulted in a dose-dependent inhibition of cell proliferation. Western blot analysis showed a decrease in cyclin D1 and an increase in p21 and p27, indicating that the mechanism of this growth inhibition is cell cycle arrest. Furthermore, SBHA treatment suppressed two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. These changes in the growth and neuroendocrine phenotype of carcinoid cells were associated with activation of the Notch1 signaling cascade. We conclude that SBHA shows promise as a potential anticancer agent for the treatment of patients with advanced carcinoid tumor disease. This paper was presented at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 19–23, 2007, Washington, DC, USA.     

p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia

In situ hybridization (ISH) assays for high-risk human papillomavirus (HR-HPV) and immunohistochemical (IHC) assays for surrogate markers such as p16 can be useful in detecting HR-HPV in cervical dysplasia, but the use of these markers in problematic cervical biopsies has not been well-established. We evaluated 3 chromogenic ISH assays (Ventana INFORM HPVII and HPVIII and DakoCytomation GenPoint) in conjunction with p16 IHC and HPV polymerase chain reaction in a study set consisting of 12 low-grade squamous intraepithelial lesions, 16 high-grade squamous intraepithelial lesions, and 30 benign cervix samples. A test set of 28 cases of atypical squamous metaplasia were also evaluated withVentana HPVIII ISH and p16 IHC. In the study set, the sensitivity of the DakoCytomation ISH assay (which detects HPV subtypes 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 68) was similar to the Ventana HPVII assay but less than that of the Ventana HPVIII ISH assay (both of which detect HPV subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) and less than p16 IHC (55.6% vs. 53.6 vs. 69.2% vs. 82.1%). All HPV ISH assays exhibited 100% specificity. p16 reactivity consisted of 2 patterns: focal strong and diffuse strong. Because focal strong p16 reactivity was identified in benign squamous epithelium (6.7% cases) and dysplastic epithelium, it was considered an equivocal result and only diffuse strong reactivity was considered to be specific for the presence of HR-HPV. In the squamous intraepithelial lesions study set, the difference in sensitivity between Ventana HPVIII ISH and p16 was not statistically significant. However, in the atypical squamous metaplasia test set cases, p16 reactivity (focal strong and diffuse strong) was significantly more sensitive than Ventana HPVIII ISH in correlating with the presence of human papillomavirus as detected by polymerase chain reaction (83.3% vs. 33.3% P=0.004). Because focal strong p16 reactivity is less specific, cases with this staining pattern are considered atypical and require further evaluation by other means. Overall, p16 IHC is considered the best candidate for the initial assessment of cervical biopsies that are histologically indeterminate for dysplasia given its wide availability, comparative ease of interpretation, and high sensitivity and specificity.