Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

Splenic infarction complicated with abscess after pelvic trauma as the first presentation of patent foramen ovale - A case report.

Hypercoagulability after trauma is a known entity. Following significant trauma, most guidelines advise anticoagulation treatment for venous thromboembolism (VTE) prophylaxis. VTE following minor trauma convoyed with arterial or systemic embolization dictate the need to search for uncommon source of thromboembolic complications. This is a report of an unusual case of pulmonary and systemic emboli complicated by splenic abscess following minor trauma in a patient with Diabetes Mellitus as the first presentation of patent foramen ovale (PFO).

Graphene-based nanocomposites for sensitivity enhancement of surface plasmon resonance sensor for biological and chemical sensing: A review.

Surface plasmon resonance (SPR) offers exceptional advantages such as label-free, in-situ and real-time measurement ability that facilitates the study of molecular or chemical binding events. Besides, SPR lacks in the detection of various binding events, particularly involving low molecular weight molecules. This drawback ultimately resulted in the development of several sensitivity enhancement methodologies and their application in the various area. Among graphene materials, graphene-based nanocomposites stands out owing to its significant properties such as strong adsorption of molecules, signal amplification by optical, high carrier mobility, electronic bridging, ease of fabrication and therefore, have established as an important sensitivity enhancement substrate for SPR. Also, graphene-based nanocomposites could amplify the signal generated by plasmon material and increase the sensitivity of molecular detection up to femto to atto molar level. This review focuses on the current important developments made in the potential research avenue of SPR and fiber optics based SPR for chemical and biological sensing. Latest trends and challenges in engineering and applications of graphene-based nanocomposites enhanced sensors for detecting minute and low concentration biological and chemical analytes are reviewed comprehensively. This review may aid in futuristic designing approaches and application of grapheneous sensor platforms for sensitive plasmonic nano-sensors.

Using a machine learning approach to predict outcome after surgery for degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is a spinal cord condition that results in progressive non-traumatic compression of the cervical spinal cord. Spine surgeons must consider a large quantity of information relating to disease presentation, imaging features, and patient characteristics to determine if a patient will benefit from surgery for DCM. We applied a supervised machine learning approach to develop a classification model to predict individual patient outcome after surgery for DCM. Patients undergoing surgery for DCM as a part of the AOSpine CSM-NA or CSM-I prospective, multi-centre studies were included in the analysis. Out of 757 patients 605, 583, and 539 patients had complete follow-up information at 6, 12, and 24 months respectively and were included in the analysis. The primary outcome was improvement in the SF-6D quality of life indicator score by the minimum clinically important difference (MCID). The secondary outcome was improvement in the modified Japanese Orthopedic Association (mJOA) score by the MCID. Predictor variables reflected information about pre-operative disease severity, disease presentation, patient demographics, and comorbidities. A machine learning approach of feature engineering, data pre-processing, and model optimization was used to create the most accurate predictive model of outcome after surgery for DCM. Following data pre-processing 48, 108, and 101 features were chosen for model training at 6, 12, and 24 months respectively. The best performing predictive model used a random forest structure and had an average area under the curve (AUC) of 0.70, classification accuracy of 77%, and sensitivity of 78% when evaluated on a testing cohort that was not used for model training. Worse pre-operative disease severity, longer duration of DCM symptoms, older age, higher body weight, and current smoking status were associated with worse surgical outcomes. We developed a model that predicted positive surgical outcome for DCM with good accuracy at the individual patient level on an independent testing cohort. Our analysis demonstrates the applicability of machine-learning to predictive modeling in spine surgery.

Herpes simplex virus delivery to orthotopic rectal carcinoma results in an efficient and selective antitumor effect.

Cancer of the rectum poses a complex therapeutic challenge because of its proximity to adjacent organs and anal sphincters. The addition of radiotherapy before surgical resection has been shown to confer good survival rates while preserving sphincter function. Nevertheless, radiation is associated with significant side effects. On the basis of our previous work showing that herpes simplex virus type-1 (HSV-1) preferentially infects human colon cancer, we set out to examine the oncolytic effect of HSV-1 on orthotopic rectal tumors in mice. Two vectors were compared for oncolytic activity, HSV-1(Gbeta) with wild-type replication and an attenuated HSV-1 vector (HSV-G47Delta). Intratumoral injection of HSV-1(Gbeta) and HSV-G47Delta resulted in a significant reduction or disappearance of the tumors and increased survival of mice. Although the use of HSV-1(Gbeta) was associated with systemic toxicity, HSV-G47Delta appears to possess a selective oncolytic activity. Moreover, infection with HSV-G47Delta resulted in the activation of the double-stranded RNA-dependent protein kinase (PKR) pathway. A significant improvement in viral replication and the antitumor effect was observed when the PKR inhibitor 2-aminopurine was coadministered with HSV-G47Delta to the tumor. In conclusion, the efficacy of local delivery of HSV-G47Delta combined with a specific chemical inhibitor of antiviral activity points to a novel therapeutic modality for rectal cancer and other solid tumors.

A novel system to study adenovirus tropism to normal and malignant colon tissues.

We describe here a new organ culture system for the evaluation of viral tropism to colon carcinomas and normal colon tissues. Organ cultures of mouse and human colon retained viability for several days and thus facilitated studies of viral tropism. Two adenoviral vectors (AD) were compared in the study: AD5, that utilizes the CAR receptor, demonstrated poor infectivity to both normal and carcinoma tissues, while a capsid-modified-AD, recognizing haparan-sulfate receptor, demonstrated efficient infectivity of both tissues. Immunohistochemistry analysis demonstrated different viral tropism; while AD5 infected only the colon epithelia, the capsid-modified-adeno infected both the epithelia and mesothelial layers. To investigate other determinants in the tissue that influence viral tropism, human cancer tissues were pretreated with collagenase and infected with the AD viruses. Increased infectivity and altered tropism were noted in the treated tumor tissue. Taken together, this ex vivo system indicated that receptor utilization and extracellular-matrix components influence AD viral tropism in solid tissues.

Urinary tract infection: is there a need for routine renal ultrasonography?

AIMS: To assess the yield of routine renal ultrasound (RUS) in the management of young children hospitalised with first uncomplicated febrile urinary tract infection (UTI). METHODS: All children aged 0-5 years who had been hospitalised over a two year period with first uncomplicated febrile UTI in a medium size institutional regional medical centre were included. Children with known urinary abnormalities and/or who had been treated with antibacterial agents within seven days before admission were excluded. All included children underwent renal ultrasonography during hospitalisation and voiding cystouretrography (VCUG) within 2-6 months. The yield of RUS was measured by its ability to detect renal abnormalities, its sensitivity, specificity, and positive and negative predictive values for detecting vesicoureteral reflux (VUR), and by its impact on UTI management. RESULTS: Of 255 children that were included in the study, 33 children had mild to moderate renal pelvis dilatation on RUS suggesting VUR, of whom only nine had VUR on VCUG. On the other hand, in 36 children with VUR on VCUG the RUS was normal. The sensitivity, specificity, positive predictive value, and negative predictive value of abnormal RUS for detecting VUR were 17.7%, 87.6%, 23.5%, and 83.2% respectively. In none of the patients with abnormal RUS was a change in the management at or following hospitalisation needed. CONCLUSION: Results show that the yield of RUS to the management of children with first uncomplicated UTI is questionable.

Role of plasmapheresis in the management of acute hepatic failure in children.

OBJECTIVE: To assess the efficacy of plasmapheresis in the treatment of children with acute hepatic failure. SUMMARY BACKGROUND DATA: Acute liver failure is expressed with severe encephalopathy, coagulopathy, and subsequent multisystem organ failure, resulting in a high death rate. Liver transplantation is considered the best option, with long-term 1-year survival rates exceeding 88%. It has been suggested that plasmapheresis may improve coagulopathy and prevent bleeding complications while maintaining adequate fluid, electrolyte, and acid-base balance. METHODS: Forty-nine patients with acute liver failure underwent a total of 243 therapeutic plasma exchanges (TPE). Indications for treatment included candidacy for liver transplant and prolonged prothrombin time. Pheresis was performed daily until the patient recovered, died, or was transplanted. Four patients were anhepatic during pheresis. RESULTS: Coagulation profiles after TPE significantly improved compared with mean preexchange values while maintaining euvolemia. No bleeding episodes were observed during the course of treatment. There was no sustained improvement in neurologic function. Spontaneous recovery was observed in three patients; the remaining either underwent transplantation (32/49) or were not considered transplant candidates because of irreversible neurologic insults (11/49) or sepsis (3/49). CONCLUSION: For children with acute liver failure, TPE is extremely effective in preventing life-threatening bleeding while maintaining appropriate volume status in small children. This method of treatment has no effect on the neurologic complications of liver failure and has no impact on the ability of the liver to regenerate.

Combined colon and hepatic resection for synchronous colorectal liver metastases.

BACKGROUND AND OBJECTIVES: The surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer remains controversial. This study was performed to assess the outcome of combined resection of colorectal cancer and liver metastases. METHODS: The perioperative data, morbidity, and survival of the patients who underwent combined colon and liver resections for synchronous colorectal liver metastases from 1988 to 1999 were compared to the parameters of the patients who underwent colon resection followed by resection of liver metastases in a staged setting. RESULTS: 198 hepatic resections were performed, of which 112 procedures in 103 patients were done for metastatic colorectal carcinoma. Twenty six patients (25%) had combined hepatic and colon resection and were compared to 86 patients with metachronous metastases who underwent colon and hepatic resection in the staging setting. Postoperative morbidity was 27 and 35%, respectively. There was no hospital mortality in the combined group vs. 2.3% in the staged group. Blood loss, intensive care unit (ICU) stay and length of postoperative stay (LOS) were similar in both groups. The 5 years cumulative survival of the group after combined surgery was 28% vs. 27% of the group after isolated hepatic resections (P = 0.21). CONCLUSION: Combined colon and hepatic resection is a safe and efficient procedure for the treatment of synchronous colorectal liver metastases. It can be performed with acceptable morbidity and no perioperative mortality. The survival after combined procedure is comparable to the one achieved after staged procedure of colon resection followed by liver resection.

Modified AdCTLA-4 vector blocks alloimmune response in vitro.

BACKGROUND: Gene transfer of the costimulatory blockade molecule CTLA-4Ig into cold-preserved rat liver allografts results in indefinite allograft survival. Despite local delivery, this mode of immunomodulation is associated with systemic immunosuppression. In an effort to restrict immunosuppression to the graft, we have constructed a novel adenoviral vector, AdCTLA-4ex-TAG, in which the Ig sequence of CTLA-4Ig DNA has been deleted to destabilize the gene product to promote rapid extrahepatic degradation while maintaining its immunosuppressive activity within the graft milieu. METHODS: (1) Vector construction. CTLA-4 extracellular binding domain (CTLA-4ex) was prepared by PCR-based cloning methods and fused in frame to a genetic element encoding an epitope TAG allowing identification of the transgene product CTLA-4exTAG. CTLA-4exTAG was subcloned into a shuttle vector enabling isolation of AdCTLA-4exTAG. (2) In vitro transfection: AdCTLA-4exTAG was transfected into MH(1)C(1) cells and then supernatant was recovered for Western blot analysis. (3) In vitro alloimmune response was characterized by CFSE proliferation assay. (4) Extrahepatic effect of AdCTLA-4exTAG was characterized by the ability to control tumor growth after implantation of a regressive, immune sensitive cancer cell line (REGb) in the skin of BDIX rats after liver transduction with AdCTLA-4exTAG. RESULTS: Expression and secretion of the recombinant protein were documented by Western blot after infection of the MH(1)C(1) cell line() with AdCTLA-4exTAG. Addition of infected MH(1)C(1) cell supernatant resulted in abrogation of alloimmune response as shown by markedly diminished division of CD4(+) T cells in a CFSE proliferation assay. Extrahepatic tumor regressed normally after liver transduction with AdCTLA-4exTAG. CONCLUSIONS: These results show efficient in vitro expression of CTLA-4exTAG after transfection with AdCTLA-4exTAG. The modified protein retains its ability to abrogate in vitro alloimmune response. Efficient control of extrahepatic tumor growth after liver-directed delivery of AdCTLA-4exTAG suggests that the immunosuppressive effect of this vector is restricted to the liver. These results set the ground for the utilization of this novel adenoviral vector in the transplant setting.

Pattern of alloimmune response in second same donor allografts after induction of tolerance using CTLA4Ig.

BACKGROUND: The pattern of allograft acceptance in the presence of costimulatory blockade is manifested by the sequential appearance of Th1 cells, followed by Th2 cells. The aim of this study was to examine whether this phenomenon repeats itself after second same donor allotransplantation, hoping to determine whether acceptance in this setting provokes a predominance of the Th2 response. METHODS: Tolerance was achieved by transplantation of CTLA4Ig-transduced ACI liver allografts in Lewis recipients. Recipient long-term survivors received a second transplant, consisting of a cervical heterotopic heart from the same ACI donor strain. Animals were sacrificed at predetermined intervals following the second transplant and the heart and liver were processed for histology and cytokine mRNA expression. RESULTS: Recipients of CTLA4Ig-transduced livers survived indefinitely. Rechallenge with same donor strain second allograft was manifested by an anergic immune response in the second cardiac allograft, and a very mild transient infiltrate within the first accepted liver graft. Cardiac function was maintained with resolution of all infiltrates. The cytokine cascade was activated within the allografts; however, the pattern of acceptance was not associated with predominance of a specific Th subtype. CONCLUSIONS: The pattern of acceptance of an allograft following CTLA4Ig-mediated costimulatory blockade is not related to long-term predominance of Th2 cells, a phenomenon that may be unique to the setting of a tolerant liver. It may be likely that the infiltrating lymphocytes that are dominant in the second graft are suppressed by other memory mechanisms.

The fate of liver grafts declined for subjective reasons and transplanted out of a local organ procurement organization.

BACKGROUND: Decisions made by transplant surgeons to decline liver grafts for local use are based on both objective and ill-defined subjective parameters. These livers may be offered and subsequently transplanted at non-local centers. We analyzed the fate of these exported livers, focusing on the outcome of grafts declined for subjective reasons. The aim is to determine whether local surgeons' concerns about inferior graft function are justified. METHODS: Over a 3-year period, 13.3% of 555 livers in our organ procurement organization (OPO) were exported and transplanted out of the local area. Donor data and reason for decline were obtained from an extensive OPO database. Objective reasons for decline were based on no appropriate matched recipient due to donor size, serologies, or malignancy with potential for spread. Subjective parameters were related to the procuring surgeon's assessment and included variables such as medical and social history, abnormal liver enzymes, older age, organ visualization, and biopsy. Recipient data were obtained from questionnaires sent to outside transplant centers. RESULTS: There was a significantly higher rate of nonfunction in the subjective group (17.1%), compared to the objective group (0%). One-year graft and patient survival were 79 and 83% for the objective group and 59 and 68% for the subjective group (P=NS). When donors declined for medical/social history were excluded from the subjective group, leaving only grafts declined based solely on the surgeon's assessment of graft quality, there is a significant difference in graft survival (79% for objective and 46% for this subjective subgroup, P=0.03). CONCLUSIONS: Livers declined for local use based on subjective assessment by the procuring surgeon have a high nonfunction rate, associated with a high morbidity. Therefore, the use of these grafts should be restricted to recipients at the most urgent status.

Mallory-Weiss syndrome: possible link to water immersion and subsequent air flight.

Mallory-Weiss Syndrome (MWS) lesions account for up to 15 per cent of upper gastrointestinal bleeding episodes. Typically these lesions present as a consequence of vomiting that is often associated with alcoholism. Recently other conditions such as pregnancy, migraine, hiatal hernia, gastric ulcer, biliary disease, and various medications have been associated with MWS. We report on a 32-year-old male who developed a MSW lesion after a prolonged period of swimming followed by an extended commercial airplane flight. The hemodynamic changes associated with swimming (increased central distribution of blood volume) and the pressure changes in commercial aircraft (a reduction of 0.3 atmospheres of pressure) are discussed. We conclude that the combination of these factors contributed to the development of a MWS lesion and gastrointestinal bleeding in this patient. We recommend that both air travel and athletic activities be considered as possible contributing factors in the evaluation of the cause of new-onset gastrointestinal bleeding.

[Laparoscopic adrenalectomy].

Constant advances and increasing experience in laparoscopic surgery renders it applicable for adrenal surgery. The wide exposure required for open adrenal surgery makes this minimally invasive procedure an attractive and advantageous alternative. Between 1996-1999, we performed 35 laparoscopic adrenalectomies in 30 patients 20-72-years old. Indications included: Conn's syndrome--14, pheochromocytoma--11, Cushing's syndrome--6, nonfunctioning adenoma--3, and metastatic sarcoma--1. 5 underwent bilateral laparoscopic adrenalectomy. In 3 (8.5%) the procedures were converted to open operations. Overall morbidity was 13% and there was no mortality. Mean operative time was 188 minutes, but only 130 in our last 10 cases. Mean hospital stay was 4 days and they returned to normal activity an average of 2 weeks later. According to our study and previous reports, laparoscopic adrenalectomy is feasible and safe and it may soon become the procedure of choice for adrenal tumors.

Duodenal duplication cyst manifested by duodeno-jejunal intussusception and hyperbilirubinemia.

A rare case of duodenal duplication cyst containing stones in a 17-year-old patient is presented. The cyst, acting as a leading point for duodeno-jejunal intussusception caused proximal small bowel obstruction and hyperbilirubinemia. Preoperative diagnosis was based on abdominal computerized tomography. At operation, the cyst wall was unroofed creating free drainage into the duodenal lumen without damaging the biliary and pancreatic ducts with resolution of symptoms.

Liver transplantation at the University of Pennsylvania and the Children's Hospital of Philadelphia.

The liver transplant program at the University of Pennsylvania and the Children's Hospital of Philadelphia experienced healthy growth in its clinical activity in the past 5 years. Patterns of referral and patient evaluation were established, care of patients while waiting on the list or being followed after transplantation was streamlined. We are now achieving excellent outcomes while transplanting relatively sicker patients. Innovative surgical procedures are implemented resulting in more efficient utilization of cadaveric and living-donor liver grafts. The protocols that are used for patient care are more standard, yet flexible and accommodate recent advancement in transplantation immunobiology. This progress of the clinical program was enhanced by careful preservation of the academic mission of the institution, which encourages the liver transplant faculty to be involved in NIH-supported clinical and basic science research.

The fate of the dropped gallstones during laparoscopic cholecystectomy.

Stones can be spilled from the gallbladder during laparoscopic cholecystectomy. These stones can be left in the peritoneal cavity or trapped at the trocar site. The potential late sequel and associated morbidity are not well documented. We reviewed the records of four patients who underwent laparoscopic cholecystectomy at Mount Sinai Medical Center in New York City who suffered from late complications attributed to gallstones left in the peritoneal cavity or abdominal wall. Four patients presented 1-14 months after laparoscopic cholecystectomy with intraabdominal and abdominal wall abscesses. The spillage of gallstones was noticed during the initial operation only in one of the patients. Three patients required laparotomy and open drainage of intraabdominal abscesses with drainage of pus and gallstones after failed attempts at percutaneous drainage. Two patients underwent local exploration of an abdominal wall abscess containing stones. Stones left in the abdominal cavity or trapped in trocar sites after laparoscopic cholecystectomy can cause serious late complications requiring repeated surgical interventions. Every effort should be made in order to avoid spillage of stones during dissection of the gallbladder and cystic duct and during retrieval of the gallbladder through the abdominal wall.