Burkholderia gladioli: five year experience in a cystic fibrosis and lung transplantation center.

BACKGROUND: The impact of infection with Burkholderia gladioli in cystic fibrosis, other chronic airway diseases and immunosuppressed patients is unknown. METHODS: A six-year retrospective review of all patients with B. gladioli infection was performed in a tertiary referral center with cystic fibrosis and lung transplantation programs. In addition, a targeted survey of all 251 lung transplant recipients was performed. Available B. gladioli isolates were analyzed via pulsed field gel electrophoresis. RESULTS: Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. No bacteremia was identified. Isolates were available in 18 patients and all were genetically distinct. Two-thirds of these isolates were susceptible to usual anti-pseudomonal antibiotics. After acquisition, only 40% of CF patients were chronically infected (> or =2 positive cultures separated by at least 6 months). Chronic infection was associated with resistance to > or =2 antibiotic groups on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. CONCLUSIONS: The majority of patients' culture positive for B. gladioli at our center have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes.     

Arterial line filtration during cardiopulmonary bypass. Neurologic, neuropsychologic, and hematologic studies

One hundred patients who underwent elective cardiac operations were randomized into two groups. Group 1 had a 20 micron nylon screen filter in the arterial line. In Group 2 no filter was used in the arterial line. Neurologic and neuropsychologic examination of the patients was performed with seven psychometric tests of the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale. These tests were conducted before and a mean of 10 days after the operation. Platelet counts and hemoglobin and total protein levels were measured at the onset and at the end of cardiopulmonary bypass. Two patients died during their hospital stay. Neurologic damage with focal signs was found in the postoperative examination in six patients (three in each group). Twenty-eight patients (28.5%) exhibited signs of mild cerebral dysfunction as assessed by the presence of archaic (primitive) reflexes. Fifteen were in Group 1 and 13 in Group 2 (no significant difference). Sixty patients (61%) had decrements greater than one standard deviation in at least one of the three tests that showed most decreased postoperative scores. There were 32 in Group 1 and 28 in Group 2 (no significant difference). When each test was analyzed individually, there were no significant differences between the two groups. Platelet counts decreased, during cardiopulmonary bypass, a mean of 33% in Group 1 and 34.5% in Group 2 (no significant difference). Both hemoglobin and total protein levels remained virtually unchanged. These results indicate that the addition of a small-pore filter in the arterial line does not prevent the neurologic and neuropsychologic disturbances frequently encountered after cardiopulmonary bypass. The filter itself does not appear to have a direct effect on the blood components. Routine use of an arterial line filter remains questionable.     

Bilateral Hematogenous Pseudomonas aeruginosa Endophthalmitis After Lung Transplantation

Pseudomonas aeruginosa commonly colonizes the airways of patients with cystic fibrosis (CF). However, the occurrence of bacteremia with metastatic infection to the eye causing endogenous endophthalmitis is very rare. In the setting of lung transplantation, the significance of P. aeruginosa bacteremia in patients with CF whose airways are colonized before transplantation is unknown. We report a case of bilateral P. aeruginosa endogenous endophthalmitis in a patient with CF after lung transplant without documented bacteremia. The patient presented with acute eye symptoms in the presence of a left atrial thrombus and the disease followed a rapidly progressive course requiring aggressive medical-surgical treatment. Typically P. aeruginosa endophthalmitis has been associated with a poor visual prognosis. However, with combined medical-surgical management this patient retained useful vision in one eye without having retinal detachment or requiring enucleation. Endogenous endophthalmitis should be considered in the differential diagnosis of ocular complaints in patients with CF after lung transplant.     

Protocols for the dosimetry of high-energy photon and electron beams: a comparison of the IAEA TRS-398 and previous international codes of practice. International Atomic Energy Agency

A new international Code of Practice for radiotherapy dosimetry co-sponsored by several international organizations has been published by the IAEA, TRS-398. It is based on standards of absorbed dose to water, whereas previous protocols (TRS-381 and TRS-277) were based on air kerma standards. To estimate the changes in beam calibration caused by the introduction of TRS-398, a detailed experimental comparison of the dose determination in reference conditions in high-energy photon and electron beams has been made using the different IAEA protocols. A summary of the formulation and reference conditions in the various Codes of Practice, as well as of their basic data, is presented first. Accurate measurements have been made in 25 photon and electron beams from 10 clinical accelerators using 12 different cylindrical and plane-parallel chambers, and dose ratios under different conditions of TRS-398 to the other protocols determined. A strict step-by-step checklist was followed by the two participating clinical institutions to ascertain that the resulting calculations agreed within tenths of a per cent. The maximum differences found between TRS-398 and the previous Codes of Practice TRS-277 (2nd edn) and TRS-381 are of the order of 1.5-2.0%. TRS-398 yields absorbed doses larger than the previous protocols, around 1.0% for photons (TRS-277) and for electrons (TRS-381 and TRS-277) when plane-parallel chambers are cross-calibrated. For the Markus chamber, results show a very large variation, although a fortuitous cancellation of the old stopping powers with the ND,w/NK ratios makes the overall discrepancy between TRS-398 and TRS-277 in this case smaller than for well-guarded plane-parallel chambers. Chambers of the Roos-type with a 60Co ND,w calibration yield the maximum discrepancy in absorbed dose, which varies between 1.0% and 1.5% for TRS-381 and between 1.5% and 2.0% for TRS-277. Photon beam calibrations using directly measured or calculated TPR20,10 from a percentage dose data at SSD = 100 cm were found to be indistinguishable. Considering that approximately 0.8% of the differences between TRS-398 and the NK-based protocols are caused by the change to the new type of standards, the remaining difference in absolute dose is due either to a close similarity in basic data or to a fortuitous cancellation of the discrepancies in data and type of chamber calibration. It is emphasized that the NK-ND,air and ND,w formalisms have very similar uncertainty when the same criteria are used for both procedures. Arguments are provided in support of the recommendation for a change in reference dosimetry based on standards of absorbed dose to water.     

Direct infant UV light exposure is associated with eczema and immune development

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Surgical management of aortic coarctation associated with ruptured cerebral artery aneurysm

We report two patients with coarctation of the aorta who were admitted to the hospital with ruptured cerebral artery aneurysms. In both patients, we surgically treated the coarctation and later repaired the intracranial lesion. One patient, a 34-year-old woman, is alive and well after 3 years; whereas, the other, a 19-year-old man, did not survive. We discuss the sequence for surgery, which continues to be subjected to debate.     

Different ovarian stimulation protocols for women with diminished ovarian reserve

Purpose To review the available treatments for women with significantly diminished ovarian reserve and assess the efficacy of different ovarian stimulation protocols. Methods Literature research performed among studies that have been published in the Pubmed, in the Scopus Search Machine and in Cohrane database of systematic reviews. Results A lack of clear, uniform definition of the poor responders and a lack of large-scale randomized studies make data interpretation very difficult for precise conclusions. Optimistic data have been presented by the use of high doses of gonadotropins, flare up Gn RH-a protocol (standard or microdose), stop protocols, luteal onset of Gn RH-a and the short protocol. Natural cycle or a modified natural cycle seems to be an appropriate strategy. Low dose hCG in the first days of ovarian stimulation has promising results. Molecular biology tools (mutations, single nucleotide polymorphisms (SNPs)) have been also considered to assist the management of this group of patients. Conclusions The ideal stimulation for these patients with diminished ovarian reserve remains a great challenge for the clinician, within the limits of our pharmaceutical quiver. Stimulation protocols commonly used for women with significantly diminished ovarian reserve.     

A review of the medicinal uses,phytochemistry and pharmacology of the genus Sapium

Ethnopharmacological relevance

Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several regions such as Malaysia, Africa, Southern China and Bolivia. Most of the species reported to possess therapeutic effects which are used for the treatment of skin-related diseases such as eczema and dermatitis, but they may also be used for overstrain, lumbago, constipation and hernia. Species of this genus are also used to treat wounds and snake bites. In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium sebiferum have/has toxic effects and are used as bird and fish poisons. This review discusses the current knowledge of the medicinal uses, phytochemistry, biological activities and toxicities of species from the genus Sapium to reveal their therapeutic potentials and gaps offering opportunities for future research.

Materials and methods

This review is based on a literature study of scientific journals and books from libraries and electronic sources, such as ScienceDirect, PubMed and ACS.

Results

As many as 65 compounds are included in this review. They belong to different classes of compounds including flavonoids, terpenoids and several other types of compounds, such as alkaloids, phenolic acids and amides. The pharmacological studies revealed that various types of preparations, extracts and single compounds of species from this genus exhibited a broad spectrum of biological activities including antioxidant, antimicrobial, anti-inflammatory and cytotoxic activities. However, Sapium glandulosum, Sapium indicum and Sapium sebiferum were reported to possess toxic effects and Sapium sebiferum was found to contain phorbol esters acting as a tumor-promoting agent.

Conclusion

The genus Sapium consists of 23 accepted (high confidence) species. However, only very few of species have been phytochemically and pharmacologically studied. There is great potential to discover new chemical constituents from this genus because only a few species have been phytochemically investigated thus far. Only 27 compounds of 65 identified compounds have been studied for their biological activities. Several extracts and single compounds from this genus were reported to exhibit interesting biological activities such as antimicrobial, antioxidant and cytotoxic effects. Furthermore, the toxicity studies of some phorbol esters suggested that the compounds acted as potential tumor-promoting agents by stimulating protein kinase C. This is an interesting fact in which a plant with medicinal properties also possesses toxic effects as well. Therefore, more clinical studies on the toxicity of the extracts of the plants and the compounds isolated from this genus are also crucial to ensure their safety and to assess their eligibility for use as sources for modern medicines.     

Invasive genetic studies in multiple pregnancy

Invasive procedures for prenatal diagnosis in multiple gestations are relatively safe and effective. First-trimester chorionic villus sampling has a lower risk of procedure failure and of fetal loss than amniocentesis but it carries a higher risk of maternal cell or twin-twin cell contamination. In experienced hands, the safety, efficacy of sampling and accuracy of genetic analysis of chorionic villus sampling and amniocentesis are similar. We describe our experience in amniocentesis, chorionic villus sampling and cordocentesis in multiple pregnancy.     

Anti-ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder whose most debilitating pathology is progressive and cumulative heterotopic ossification (HO) of skeletal muscles, ligaments, tendons, and fascia. FOP is caused by mutations in the type I BMP receptor gene ACVR1, which enable ACVR1 to utilize its natural antagonist, activin A, as an agonistic ligand. The physiological relevance of this property is underscored by the fact that HO in FOP is exquisitely dependent on activation of FOP-mutant ACVR1 by activin A, an effect countered by inhibition of anti–activin A via monoclonal antibody treatment. Hence, we surmised that anti-ACVR1 antibodies that block activation of ACVR1 by ligands should also inhibit HO in FOP and provide an additional therapeutic option for this condition. Therefore, we generated anti-ACVR1 monoclonal antibodies that block ACVR1’s activation by its ligands. Surprisingly, in vivo, these anti-ACVR1 antibodies stimulated HO and activated signaling of FOP-mutant ACVR1. This property was restricted to FOP-mutant ACVR1 and resulted from anti-ACVR1 antibody–mediated dimerization of ACVR1. Conversely, wild-type ACVR1 was inhibited by anti-ACVR1 antibodies. These results uncover an additional property of FOP-mutant ACVR1 and indicate that anti-ACVR1 antibodies should not be considered as therapeutics for FOP.