Photodynamic Therapy of Necrobiosis Lipoidica - A Multicenter Study of 18 Patients

Background: Necrobiosis lipoidica (NL) is a granulomatous skin disease of unknown origin, and no reliably effective treatment option exists to handle this often disfiguring disease. Recently, a patient with long-lasting NL was reported to be cured by topical photodynamic therapy (PDT). Objective: To evaluate the overall potential of PDT in the treatment of NL on the lower legs. Methods: Retrospective study of 18 patients (aged 16 - 62 years) from 3 European university departments of dermatology treated with PDT for NL. Methyl aminolevulinate or 5-aminolevulinic acid were used as topically applied photosensitizers. Illumination followed with red light-emitting diode light. Results: Complete response was seen in 1/18 patients after 9 PDT cycles, and partial response in 6/18 patients (2 - 14 PDT cycles) giving an overall response rate of 39% (7/18). Conclusion: Although almost 40% of the cases showed some degree of response, PDT cannot currently be recommended as first-line therapy of NL. Subpopulations of therapy-resistant NL patients may, however, benefit from PDT. Copyright (C) 2008 S. Karger AG, Base

Risk of cardio-respiratory abnormalities in preterm infants placed in car seats: a cross-sectional study

BACKGROUND: Little is known about the factors that predispose to the occurrence and severity of cardio-respiratory symptoms during the placement of a prematurely born infant in a car seat. The impact of gestational age, weight at discharge and infant's pre-existing cardio-respiratory status (in the supine position) on cardio-respiratory function during pre-discharge testing in a car seat (semi-upright position) has not been investigated. METHODS: The cardio-respiratory function of 42 preterm neonates with gestational age 24 to 35 weeks and discharge weight 1790 to 2570 grams were monitored for 45 minutes before, during, and after placement in a car seat. The occurrence of periodic breathing, apnea, bradycardia, or decreased oxygen saturation (SaO2) was analyzed. RESULTS: Prior to the car seat testing, 15 (35.7%) infants displayed one or more abnormalities of cardio-respiratory function. During the car seat testing, 25 (59.6%) infants had periodic breathing, 33 (78.2%) had oxygen saturation <90%, 14 (33.3%) had bradycardia less than 80 beats per minute, and 35 (83.3%) had a combination of these symptoms. Infants, both with and without pre-existing cardio-respiratory abnormalities, had an almost equal probability (80% vs. 83.3%) for the development of cardio-respiratory symptoms during placement in the car seat. Weight at discharge ([less than or equal to] 2,000 grams) but not the gestational age (<28 weeks or [greater than or equal to] 28<37 weeks), was associated with either increased episodes of oxygen desaturation or the combination of cardio-respiratory symptoms that were seen during the placement of these infants in the car seat. Repositioning from the car seat to the supine position showed normalization of cardio-respiratory function in the majority (83%) of the tested infants. None of the tested clinical factors were associated with the severity of the cardio-respiratory symptoms. CONCLUSION: Pre-discharge testing of the cardio-respiratory function of preterm infants during placement in a car seat is important for the prevention of cardio-respiratory symptoms during their transportation. However, the high risk for developing cardio-respiratory symptoms will require the consideration of an alternative mode of safe home transportation for preterm infants; especially those with a discharge weight less than 2,000 grams

Management of neonatal hyperbilirubinemia: Pediatricians' practices and educational needs

BACKGROUND: Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994. METHODS: A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia. RESULTS: The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37–38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility. CONCLUSION: The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern

Measurement and monitoring of electrocardiogram belt tension in premature infants for assessment of respiratory function

Background: Monitoring of the electrocardiogram (ECG) in premature infants with conventional adhesive-backed electrodes can harm their sensitive skin. Use of an electrode belt prevents skin irritation, but the effect of belt pressure on respiratory function is unknown. A strain gauge sensor is described which measures applied belt tension. Method: The device frame was comprised of an aluminum housing and slide to minimize the device weight. Velcro tabs connected housing and slide to opposite tabs located at the electrode belt ends. The slide was connected to a leaf spring, to which were bonded two piezoresistive transducers in a half-bridge circuit configuration. The device was tested for linearity and calibrated. The effect on infant respiratory function of constant belt tension in the normal range (30 g–90 g) was determined. Results: The mechanical response to a step input was second order (f_n = 401 Hz, ζ = 0.08). The relationship between applied tension and output voltage was linear in the range 25–225 gm of applied tension (r² = 0.99). Measured device sensitivity was 2.18 mV/gm tension using a 5 V bridge excitation voltage. When belt tension was increased in the normal range from 30 gm to 90 gm, there was no significant change in heart rate and most respiratory functions during monitoring. At an intermediate level of tension of 50 gm, pulmonary resistance and work of breathing significantly decreased. Conclusion: The mechanical and electrical design of a device for monitoring electrocardiogram electrode belt tension is described. Within the typical range of application tension, cardiovascular and respiratory function are not substantially negatively affected by electrode belt force

European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring = 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN

International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Background: Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. Methods: The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. Results: In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. Conclusions: Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation

Panmicrobial Oligonucleotide Array for Diagnosis of Infectious Diseases

To facilitate rapid, unbiased, differential diagnosis of infectious diseases, we designed GreeneChipPm, a panmicrobial microarray comprising 29,455 sixty-mer oligonucleotide probes for vertebrate viruses, bacteria, fungi, and parasites. Methods for nucleic acid preparation, random primed PCR amplification, and labeling were optimized to allow the sensitivity required for application with nucleic acid extracted from clinical materials and cultured isolates. Analysis of nasopharyngeal aspirates, blood, urine, and tissue from persons with various infectious diseases confirmed the presence of viruses and bacteria identified by other methods, and implicated Plasmodium falciparum in an unexplained fatal case of hemorrhagic feverlike disease during the Marburg hemorrhagic fever outbreak in Angola in 2004–2005

Comprehensive viral oligonucleotide probe design using conserved protein regions

Oligonucleotide microarrays have been applied to microbial surveillance and discovery where highly multiplexed assays are required to address a wide range of genetic targets. Although printing density continues to increase, the design of comprehensive microbial probe sets remains a daunting challenge, particularly in virology where rapid sequence evolution and database expansion confound static solutions. Here, we present a strategy for probe design based on protein sequences that is responsive to the unique problems posed in virus detection and discovery. The method uses the Protein Families database (Pfam) and motif finding algorithms to identify oligonucleotide probes in conserved amino acid regions and untranslated sequences. In silico testing using an experimentally derived thermodynamic model indicated near complete coverage of the viral sequence database

Inferred Biomolecular Interaction Server—a web server to analyze and predict protein interacting partners and binding sites

IBIS is the NCBI Inferred Biomolecular Interaction Server. This server organizes, analyzes and predicts interaction partners and locations of binding sites in proteins. IBIS provides annotations for different types of binding partners (protein, chemical, nucleic acid and peptides), and facilitates the mapping of a comprehensive biomolecular interaction network for a given protein query. IBIS reports interactions observed in experimentally determined structural complexes of a given protein, and at the same time IBIS infers binding sites/interacting partners by inspecting protein complexes formed by homologous proteins. Similar binding sites are clustered together based on their sequence and structure conservation. To emphasize biologically relevant binding sites, several algorithms are used for verification in terms of evolutionary conservation, biological importance of binding partners, size and stability of interfaces, as well as evidence from the published literature. IBIS is updated regularly and is freely accessible via http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html