Measurement of 227Ac impurity in 225Ac using decay energy spectroscopy.

225Ac is a valuable medical radionuclide for targeted α therapy, but 227Ac is an undesirable byproduct of an accelerator-based synthesis method under investigation. Sufficient detector sensitivity is critical for quantifying the trace impurity of 227Ac, with the 227Ac/225Ac activity ratio predicted to be approximately 0.15% by end-of-bombardment (EOB). Superconducting transition edge sensor (TES) microcalorimeters offer high resolution energy spectroscopy using the normal-to-superconducting phase transition to measure small changes in temperature. By embedding 225Ac production samples in a gold foil thermally coupled to a TES microcalorimeter we can measure the decay energies of the radionuclides embedded with high resolution and 100% detection efficiency. This technique, known as decay energy spectroscopy (DES), collapses several peaks from α decays into single Q-value peaks. In practice there are more complex factors in the interpretation of data using DES, which we will discuss herein. Using this technique we measured the EOB 227Ac impurity to be (0.142 ± 0.005)% for a single production sample. This demonstration has shown that DES is a useful tool for quantitative measurements of complicated spectra.

Measuring colposcopy quality in Canada: development of population-based indicators.

Background: Colposcopy is a key part of cervical cancer control. As cervical cancer screening and prevention strategies evolve, monitoring colposcopy performance will become even more critical. In the present paper, we describe population-based colposcopy quality indicators that are recommended for ongoing measurement by cervical cancer screening programs in Canada. Methods: The Pan-Canadian Cervical Cancer Screening Network established a multidisciplinary expert working group to identify population-based colposcopy quality indicators. A systematic literature review was conducted to ascertain existing population and program-level colposcopy quality indicators. A systems-level cervical cancer screening pathway describing each step from an abnormal screening test, to colposcopy, and back to screening was developed. Indicators from the literature were assigned a place on the pathway to ensure that all steps were measured. A prioritization matrix scoring system was used to score each indicator based on predetermined criteria. Proposed colposcopy quality indicators were shared with provincial and territorial screening programs and subsequently revised. Results: The 10 population-based colposcopy quality indicators identified as priorities were colposcopy uptake, histologic investigation (biopsy) rate, colposcopy referral rate, failure to attend colposcopy, treatment frequency in women 18-24 years of age, re-treatment proportion, colposcopy exit-test proportion, histologic investigation (biopsy) frequency after low-grade Pap test results, length of colposcopy episode of care, and operating room treatment rate. Two descriptive indicators were also identified: colposcopist volume and number of colposcopists per capita. Summary: High-quality colposcopy services are an essential component of provincial cervical cancer screening programs. The proposed quality and descriptive indicators will permit colposcopy outcomes to be compared between provinces and across Canada so as to identify opportunities for improving colposcopy services.

Elevated ST2 Distinguishes Incidences of Pediatric Heart and Small Bowel Transplant Rejection.

Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0.0002). SBTx recipients also displayed increased serum sST2 during incidences of rejection (7536 ± 1561 vs. 2662 ± 543.8 pg/mL; p = 0.0347). Receiver operator characteristic (ROC) analysis showed that serum sST2 > 600 pg/mL could discriminate time points of HTx rejection and nonrejection (area under the curve [AUC] = 0.724 ± 0.053; p = 0.0003). ROC analysis of SBTx measures revealed a similar discriminative capacity (AUC = 0.6921 ± 0.0820; p = 0.0349). Quantitative evaluation of both HTx and SBTx biopsies revealed that rejection significantly increased allograft ST2 expression. Pathway and Network Analysis of biopsy data pinpointed ST2 in the dominant pathway modulated by rejection and predicted tumor necrosis factor-α and IL-1ß as upstream activators. In total, our data indicate that alloimmune-associated pro-inflammatory cytokines increase ST2 during rejection. They also demonstrate that routine serum sST2 quantification, potentially combined with other biomarkers, should be investigated further to aid in the noninvasive diagnosis of rejection.

Parvovirus associated fulminant hepatic failure and aplastic anemia treated successfully with liver and bone marrow transplantation. A report of two cases.

Aplastic anemia (AA) has been observed in nearly a third of patients undergoing liver transplantation (LT) for non-A-E fulminant hepatic failure (FHF). Few of these patients have been successfully managed with sequential LT and bone marrow transplantation (BMT). No causative agent has been identified for the FHF or AA in these reported cases. At our center, two patients, aged 15 years and 7 years, respectively, underwent sequential living-related LT and living-unrelated BMT. These patients are 10/9 years and 5/4 years post-LT/BMT. Human parvovirus B19 (HPV-B19) was established as the causative agent for FHF in both these patients by polymerase chain reaction. This report presents the first two cases associating HPV-B19 with FHF and AA who underwent sequential LT and BMT with excellent outcomes.

Staphylococcus aureus infections after liver transplantation.

BACKGROUND: More data on the risk factors and outcomes after Staphylococcus aureus infections in liver transplantation are needed. METHODS: Liver recipients with S. aureus infections (cases) were retrospectively identified and compared to gender-, age-, and transplant type-matched (1:2) non-S. aureus-infected controls. Risk factors associated with S. aureus infections were identified by conditional logistic regression analysis. RESULTS: We evaluated 51 patients (median age 52 years). First S. aureus infections developed at a median time of 29 days after transplantation, with 52.94% of them in the first month; 88.24% were nosocomial, 41.18% were polymicrobial, and 47.06% were caused by methicillin-resistant S. aureus (MRSA). Surgical site infections represented 58.82% and bacteremia 23.53%. By univariate analysis, patients with S. aureus infections were intubated more frequently (odds ratio [OR] 26.92, 95% confidence interval [CI] 3.23-3,504.15, p = 0.0006), had a central line (OR 11.69, 95% CI 1.42-95.9, p = 0.02), or recent surgery (OR 26.92, 95% CI 3.23-3,504.15, p = 0.0006) compared with controls. By multivariate analysis, subjects who underwent surgery within 2 weeks prior to infection had a 26.9 times higher risk of developing S. aureus infection (95% CI 3.23-3,504.15, p = 0.0006); these results were adjusted for matched criteria. S. aureus infections did not affect graft or patient survival, but the study was not powered for such outcomes. CONCLUSION: Only recent surgical procedure was found to be a significant independent risk factor for S. aureus infections after liver transplantation.

The course of the distal saphenous nerve: a cadaveric investigation and clinical implications.

INTRODUCTION: Injury to the saphenous nerve at the ankle has been described as a complication resulting from incision and dissection over the distal tibia and medial malleolus. However, the exact course and location of the distal saphenous nerve is not well described in the literature. The purpose of this study was to determine the distal limit of the saphenous nerve and its anatomic relationship to commonly identified orthopaedic landmarks and surgical incisions. METHODS: Sixteen cadaveric ankles were examined at the level of the distal tibia medial malleolus. An incision was made along the medial aspect of the lower extremity from the knee to the hallux to follow the course and branches of the saphenous nerve under direct visualization. We recorded the shortest distance from the most distal visualized portion of the saphenous nerve to the tip of the medial malleolus, to the antero-medial arthroscopic portal site, and to the tibialis anterior tendon. RESULTS: The saphenous nerve runs posterior to the greater saphenous vein in the leg and divides into an anterior and posterior branch approximately 3 cm proximal to the tip of the medial malleolus. These branches terminate in the integument proximal to the tip of the medial malleolus, while the vein continues into the foot. The anterior branch ends at the anterior aspect of the medial malleolus near the posterior edge of the greater saphenous vein. The posterior branch ends near the posterior aspect of the medial malleolus. The average distance from the distal-most visualized aspect of the saphenous nerve to the tip of the medial malleolus measured 8mm +/-; 5mm; from the nerve to the medial arthroscopic portal measured 14mm +/-2mm; and from the nerve to the tibialis anterior measured 16mm +/-3mm. In only one case (of 16) was there an identifiable branch of the saphenous nerve extending to the foot and in this specimen it extended to the first metatarsophalangeal joint. The first metatarsophalangeal joint was innervated by the superficial peroneal nerve in all cases. Small variations were also noted. DISCUSSION AND CONCLUSIONS: This study highlights the proximity of the distal saphenous nerve to common landmarks in orthopaedic surgery. This has important clinical implications in ankle arthroscopy, tarsal tunnel syndrome, fixation of distal tibia medial malleolar fractures, and other procedures centered about the medial malleolus. While the distal course of the saphenous nerve is generally predictable, variations exist and thus the orthopaedic surgeon must operate cautiously to prevent iatrogenic injury. To avoid saphenous nerve injury, incisions should stay distal to the tip of the medial malleolus. The medial arthroscopic portal should be more than one centimeter from the anterior aspect of the medial malleolus which will also avoid the greater saphenous vein. Incision over the anterior tibialis tendon should stay within one centimeter of the medial edge of the tendon.

The extensor tendon splitting approach to the proximal interphalangeal joint: do we need to reinsert the central slip?

Current approaches to the proximal interphalangeal (PIP) joint have potential complications and limitations. We present a dorsal approach that involves splitting the extensor tendon in the midline, detaching the insertion of the central slip and repairing the extensor tendon without reinserting the tendon into the base of the middle phalanx. A retrospective review of 16 digits that had the approach for a PIP joint arthroplasty with a mean follow up of 23 months found a postoperative PIP active ROM of 61 degrees (range 25-90 degrees). Fourteen digits had no extensor lag, while two digits had an extensor lag of 20 degrees and 25 degrees. This modified approach is fast and simple and does not cause an extensor lag.

A reliable and safe gastrotomy closure technique assessed in a porcine survival model pilot study: success of the Queen's closure.

BACKGROUND AND STUDY AIMS: The evolution of NOTES to clinical implementation has been hampered by lack of a reliable, safe, and easy-to-implement technique for closure of the opening created in accessing the peritoneum. The Queen's closure uses a combination of endoscopic clips and loop devices to seal such defects in the stomach wall. This study aimed to assess the Queen's closure in a porcine survival model. METHODS: Five 30-kg pigs underwent endoscopic transgastric surgery with exploration of the peritoneum. The endoscope was then withdrawn back into the stomach and the closure performed. The animals were recovered, monitored closely, and underwent endoscopy 1 week after surgery. They were then euthanized at 2 (n = 2) and 3 (n = 3) weeks after surgery with subsequent necropsy. RESULTS: The mean procedure time (from intubation of the esophagus to withdrawal of the endoscope) was 79 minutes (range 45-105 minutes) with a mean time of exploration of the peritoneum of 14 minutes (range 8-25 minutes). All animals recovered well with no apparent pain, distress, or signs of infection. Endoscopic examination 1 week after surgery revealed all the closures to be intact and only identifiable by a small ulcer. At necropsy, the gastrotomy site was identifiable only by minor serosal adhesions. Histological study demonstrated full-thickness closure with minimal inflammation. CONCLUSIONS: The Queen's closure is a reliable and safe technique that provides full-thickness gastrotomy closure without any observed complications. The technique has proven to be transferable knowledge that holds promise for clinical implementation.

The Queen's closure: a novel technique for closure of endoscopic gastrotomy for natural-orifice transluminal endoscopic surgery.

BACKGROUND AND AIMS: Finding a reliable, safe, adaptable method of closing gastrotomies for natural-orifice transluminal endoscopic surgery (NOTES) procedures has been a major challenge facing this new clinical area. The Queen's NOTES Group has designed a novel endoscopic method of closing gastrotomies which involved using PolyLoop polyp ligature devices and endoscopic clips. The current study describes the technique and a pilot study of leak testing it versus hand-sewn suture closure. METHODS: Ten fresh pig stomachs were used, five for each technique. A 16-mm endoscopic gastrotomy was performed on the anterior wall of each. Five stomachs were then closed using the Queen's closure technique, and five with a hand-sewn double-layer suture technique. The stomachs were then connected to a water infusion device with sensitive pressure monitoring and were filled until leakage was detected at the closure site. RESULTS: The closures were all technically successful. The mean time for each gastrotomy and closure using the Queen's closure technique was 1.2 hours. The mean leak pressure for the Queen's closure was 51.8 mmHg and for the hand-sewn suture technique it was 80.8 mmHg ( P < 0.001). CONCLUSIONS: The Queen's closure technique holds promise as a reliable transferable technique for closing gastrotomies. Further study is necessary to evaluate its effects in live models.

Self-implanted artificial nodules: a computed tomography mimic of penile pathology.

Self-introduction of foreign bodies along the penile shaft has been reported in several ethnic and social groups, mainly in Asia, and recently has been described in Europe. We present the case of a 34-year-old homeless Russian immigrant who had an abdominal CT performed during an emergency department visit. On the CT scan, several hyperdense, well-demarcated subcutaneous nodules along the penile shaft were noted. Following a focused history and physical examination, the nodules were found to represent artificial foreign bodies made of glass, which were self-introduced by the patient in order to allegedly increase the pleasure of sexual partners. Penile nodules may be a manifestation of diverse pathological entities including infectious, inflammatory, and neoplastic processes. It is important for the radiologist to be familiar with this social phenomenon and its radiological appearance in order to avoid erroneous diagnosis.

The sandwich omental flap for abdominal wall defect reconstruction.

We present a case of a large full thickness abdominal wall defect following excision of a huge basal cell carcinoma, uniquely reconstructed with a sandwich omental flap, vicryl/prolene (vypro II) mesh and split thickness skin graft.

Oxidative stress in colon tissue induced by vitamin E depletion.

Inflammatory disorders of the bowel and colon cancer are associated with elevated indices of oxidative stress. Analogous elevations in markers of oxidative stress and loss of cell-membrane integrity are also observed in the colons of rats deficient in vitamin E (D-alpha-tocopherol), the major lipid-soluble antioxidant in biological systems. The causal relationship between colon pathologies associated with oxidative stress and dietary deficiency in antioxidant vitamins such as vitamin E is still uncertain. Investigation of potential mechanisms by which lack of dietary vitamin E may lead to clinically relevant pathological changes in colon tissue was conducted using gene expression profiling strategies on vitamin E-sufficient and -deficient rats. Morphological changes and increased indices of lipid peroxidation were linked to vitamin E deficiency. These changes in colon tissue are potentially important in disease pathogenesis of the colon linked with oxidative stress or other direct consequences of inadequate levels of vitamin E.

Malignant melanoma metastasis to the sentinel node in the popliteal fossa.

Malignant melanoma metastasis to regional nodes is a well-recognised clinical event. Increasingly, sentinel lymph-node biopsy is being advocated for diagnostic and prognostic purposes. The lymphatic spread of tumour from the lateral aspect of the lower leg and foot is classically described as draining directly to the groin. We discuss the role of lymphoscintigraphy and popliteal dissection with reference to a recent case of a patient with a malignant melanoma at the level of the lateral malleolus that was shown to drain directly to a sentinel node in the popliteal fossa.

Patient evaluation and management with selective use of magnetic resonance cholangiography and endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy.

OBJECTIVE: To assess the utility of triage guidelines for patients with cholelithiasis and suspected choledocholithiasis, incorporating selective use of magnetic resonance cholangiography (MRC) and endoscopic retrograde cholangiopancreatography (ERCP) before laparoscopic cholecystectomy (LC). SUMMARY BACKGROUND DATA: ERCP is the most frequently used modality for the diagnosis and resolution of choledocholithiasis before LC. MRC has recently emerged as an accurate, noninvasive modality for the detection of choledocholithiasis. However, useful strategies for implementing this diagnostic modality for patient evaluation before LC have not been investigated. METHODS: During a 16-month period, the authors prospectively evaluated all patients before LC using triage guidelines incorporating patient information obtained from clinical evaluation, serum chemistry analysis, and abdominal ultrasonography. Patients were then assigned to one of four groups based on the level of suspicion for choledocholithiasis (group I, extremely high; group 2, high; group 3, moderate; group 4, low). Group 1 patients underwent ERCP and clearance of common bile duct stones; group 2 patients underwent MRC; group 3 patients underwent LC with intraoperative cholangiography; and group 4 patients underwent LC without intraoperative cholangiography. RESULTS: Choledocholithiasis was detected in 43 of 440 patients (9.8%). The occurrence of choledocholithiasis among patients in the four groups were 92.6% (25/27), 32.4% (12/37), 3.8% (2/52), and 0.9% (3/324) for groups 1, 2, 3, and 4, respectively (P <.001). MRC was used for 8.4% (37/440) of patients. Patient triage resulted in the identification of common bile duct stones during preoperative ERCP in 92.3% (36/39) of the patients. Unsuspected common bile duct stones occurred in six patients (1.4%). CONCLUSIONS: The probability of choledocholithiasis can be accurately assessed based on information obtained during the initial noninvasive evaluation. Stratification of risks for choledocholithiasis facilitates patient management with the most appropriate diagnostic studies and interventions, thereby improving patient care and resource utilization.

Nitric oxide synthase inhibition negates bombesin-induced gastroprotection.

BACKGROUND: Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. METHODS: Rats were given subcutaneous saline or bombesin (10-100 microg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm(2)). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. RESULTS: Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) l-arginine (300 mg/kg), but not d-arginine, abolished the effects of l-NAME. CONCLUSIONS: Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

The role of protein kinase A in anaerobic energy production during liver storage.

BACKGROUND/AIM: During cold liver storage in University of Wisconsin solution, glycolysis is inhibited by declining intracellular pH and a reduction in glycogen phosphorylase activity. The current study investigated the effects of a histidine-buffered, modified University of Wisconsin solution with cyclic-AMP analogue plus phosphodiesterase inhibitors to optimize both pH and PK A-mediated limits on glycolytic energy production. METHODS: In an isolated rodent-liver system, dioctanoyl-cAMP was supplemented with each phosphodiesterase inhibitor (isobutylmethylxanthine, papaverine, Ro 20-1724, dipyridamole). Once the most efficacious combination was determined, a separate group of livers was cold-stored for 24 h and then reperfused at 37 degrees C to examine regeneration of high energy adenylates. RESULTS: Lactate accumulation in the histidine-lactobionate-raffinose group was 8.7 micromol/g; net increases were greater with all four phosphodiesterase inhibitors with dioctanoyl-cAMP; dipyridamole resulted in a maximum increase of 16.7 micromol/g. ATP was consistently higher in all treatment groups with phosphodiesterase inhibitors throughout 24 h; even after 10-24 h, levels with dipyridamole-treatment were 250-280% higher than with University of Wisconsin (p<0.05). Assessment of glycogen phosphorylase activity in the dipyridamole-treatment group indicated that increased glycolytic activity over the first 4 h was a direct consequence of elevated enzyme levels. However, between 4-10 h, phosphofructokinase underwent a phosphorylation, leading to an inhibition at this point in glycolysis. Upon reperfusion, the higher ATP/ADP and ADP/ AMP ratios found with phosphodiesterase inhibitor treatment suggested that adenylate regeneration was superior with dipyridamole+dioctanoyl-cAMP. CONCLUSION: Dipyridamole plus dioctanoyl-cAMP treatment achieved increased glycogenolysis throughout 24 h storage by maintaining glycogen phosphorylase in a phosphorylated (active) state; however, a PK A-mediated phosphorylation (inhibition) of phosphofructokinase resulted in decreased glycolytic ATP production between 4-10 h.

Epidemic diphtheria in Ukraine, 1991-1997.

In 1991, Ukraine experienced a return of epidemic diphtheria after decades of control that had resulted in <40 sporadic cases reported every year. Increased incidence was first recorded in Kiev, Lviv, and Odessa. By 1993, the epidemic had spread to >50% of the oblasts (provinces) in the country, and by 1995, all regions were affected. In 1995, at the peak of the epidemic, >5,000 cases and >200 deaths were reported. As in Russia, >80% of these cases were diagnosed in persons 16-59 years old. In 1993, the government of Ukraine initiated a program of increased immunization among children and at-risk adults, and by 1995, a mass immunization strategy was adopted in an effort to arrest the epidemic, which was increasing exponentially. In 1996, the number of cases started to decrease, and data from 1998 indicate that the downward trend has continued. It is likely that the diphtheria epidemic in Ukraine started among children, who had been left vulnerable due to inadequate childhood immunizations, and then quickly spread to inadequately protected adults.

Comparison of intra-articular fentanyl and intra-articular bupivacaine for post-operative pain relief after knee arthroscopy.

A randomized double-blinded study consisting of 107 patients was conducted to compare the effect on post-operative pain relief of intra-articular fentanyl and intra-articular bupivacaine after knee arthroscopy. The results showed that intra-articular bupivacaine produced superior analgesia in the immediate post-operative period. At 2 h post-operatively, the intra-articular bupivacaine group had a mean pain score of 2.0 (standard deviation 2.1, P < 0.05) compared with the intra-articular fentanyl group which had a mean pain score of 3.2 (standard deviation 2.3, P < 0.05). After 2 h post-operatively, intra-articular bupivacaine and intra-articular fentanyl had a similar effect on pain scores. The mean pain score 18 h post-operatively was 2.7 for the intra-articular bupivacaine group (standard deviation 2.2, P value 0.6) compared with the intra-articular fentanyl group which had a mean pain score of 2.8 (standard deviation 1.9, P value 0.6).