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Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies.

BACKGROUND: Inflammatory choriocapillaropathies (choriocapillaritis) correspond to the clinical spectrum of lesions of the fundus, including acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis (MC), and other rarer entities caused by inflammatory disturbances of choriocapillaris perfusion. The aim here was to study the sensitivity of indocyanine green (ICG) angiography in investigating and following inflammatory choriocapillaropathies. PATIENTS AND METHODS: Patients with inflammatory choriocapillaropthies were included who had had a dual fluorescein and ICG angiography as well as visual field testing (Goldman or computerized perimetry) at presentation and on follow-up visits. ICG angiography was performed according to a routine angiographic protocol used for inflammatory diseases and was correlated with fundus examination, fluorescein angiography, and visual field testing. RESULTS: Three patients with MEWDS, two with APMPPE, and two with MC were included. The visual field alterations in all seven patients were well correlated with the extent of the hypofluorescent areas seen on ICG angiography, whereas they were badly correlated with fluorescein angiographic signs and their evolution. The visual field in MEWDS was particularly well correlated with the importance of peripapillary hypofluorescence seen on ICG angiography. In MC, the evolution of new lesions was well demonstrated by ICG angiography and well correlated with visual symptoms and visual fields, but was barely detected on fundus examination and by fluorescein angiography. CONCLUSIONS: ICG angiographic signs were shown to be closely correlated with visual function (visual field testing). This was not the case for either fundus examination or fluorescein angiography. ICG angiography appears as a very sensitive follow-up parameter in inflammatory choriocapillaropathies, giving morphological information on the evolution of the disease and on the response to treatment when therapy is indicated.

Adult↗

Informal and formal caregivers' involvement in nursing home care activities: impact of integrated care.

AIMS: This paper reports a study to investigate the relationships between informal and formal care, changing relationships over time, impact of integrated care, and theoretical and methodological lessons that can be drawn from research on this topic. BACKGROUND: The ratio of informal to formal care provided in nursing homes varies. In many countries the predominance of traditional, formal care is being challenged by the emergence of integrated care models in which formal and informal caregivers co-operate and co-ordinate their activities to deliver tailor-made care. This move towards integrated care is likely to result in changes in the degree and nature of involvement of formal and informal caregivers in care activities. However, very little research has investigated this. Previous research is restricted to one point in time, as opposed to focussing on the changing relationships between formal and informal caregivers over time. METHODS: The quasi-experimental design encompassed a traditional care comparison setting and an experimental setting with an integrated care intervention. At three measurement points, one before the intervention in May/June 2000 and two at 6 and 14 months after the intervention, informal and formal caregivers recorded their care activities. Informal care relationships were determined by calculating contribution rates and informal/formal care ratios for 14 activities. RESULTS: Integrated care did not bring about the expected major changes. There was a limited amount of substitution of formal care with informal care. There were limited changes in the extent of dual specialization, in which informal and formal caregivers perform separate activities. There was little supplementation of formal care with informal care. Furthermore, relationships changed over time, resulting in a complex pattern of linkages at the level of separate activities. CONCLUSIONS: Informal caregivers contribute to many activities. The impact of integrated care on the degree and nature of involvement, however, was moderate. A possible explanation is the contextual situation for nursing home care. These findings point to the need for further research into the (changing) relationship between formal and informal carers in residential care activities and the evolution of this relationship over time.

Caregivers↗

Mapping of 13 horse genes by fluorescence in-situ hybridization (FISH) and somatic cell hybrid analysis.

We report fluorescence in-situ hybridization (FISH) and somatic cell hybrid mapping data for 13 different horse genes (ANP, CD2, CLU, CRISP3, CYP17, FGG, IL1RN, IL10, MMP13, PRM1, PTGS2, TNFA and TP53). Primers for PCR amplification of intronic or untranslated regions were designed from horse-specific DNA or mRNA sequences in GenBank. Two different horse bacterial artificial chromosome (BAC) libraries were screened with PCR for clones containing these 13 Type I loci, nine of which were found in the libraries. BAC clones were used as probes in dual colour FISH to confirm their precise chromosomal origin. The remaining four genes were mapped in a somatic cell hybrid panel. All chromosomal assignments except one were in agreement with human-horse ZOO-FISH data and revealed new and more detailed information on the equine comparative map. CLU was mapped by synteny to ECA2 while human-horse ZOO-FISH data predicted that CLU would be located on ECA9. The assignment of IL1RN permitted analysis of gene order conservation between HSA2 and ECA15, which identified that an event of inversion had occurred during the evolution of these two homologous chromosomes.

Animals↗

[Infectious mononucleosis: study on hospitalized children].

OBJECTIVES: To analyze the patients diagnosed of infectious mononucleosis (IM) in our institution, in order to study the symptoms and clinical evolution. MATERIAL AND METHOD: We retrospectively analyse 37 hospitalized children aged between 3 months and 14 years. Diagnosed of IM by production of immunoglobulin M (IgM) to viral capsid antigen (VCA). RESULT: In our series of 37 children, 14 were less than 4 years old. Among clinical data, lymphadenopathy (86%), fever (81%) and pharyngotonsillitis (70%) were the more striking. We found jaundice only in three of the older children. Upper airways obstruction was common, and specially severe in young children. Three patients developed pneumonia during the disease course. Only ten patients produced heterophile antibodies. Two children showed dual antibody rises to Epstein-Barr virus and cytomegalovirus. Corticotherapy was used in 7 children. The complications are presented in 68% of patients. CONCLUSIONS: Clinical aspects of IM were similar to those in the young adult, and complications occur more frequently. We found lack of heterophile antibodies, more frequent in youngest.

Child↗

Use of a new type of PTFE mesh in laparoscopic incisional hernia repair: the continuing evolution of technique and surgical expertise.

We present the results of our first 44 laparoscopic incisional hernia repairs. This study examines the effectiveness of this technique in patients presenting with a first-time or recurrent incisional hernia. From October 2001 to November 2002, a total of 45 consecutive patients underwent laparoscopic incisional hernia repair with a new form of expanded polytetrafluoroethylene (ePTFE) mesh. Patient data, preoperative, intraoperative, and postoperative records, were recorded and analyzed. Mean defect size was 84 cm2, mean mesh size was 311 cm2, mean surgical time was 65 minutes, and mean hospital stay was 2.25 days. Postoperative complications occurred in four patients (9.1%). The laparoscopic approach is a safe, effective, and relatively complication-free option in the management of first-time and recurrent incisional hernias. The use of modified ePTFE mesh with a dual surface in incisional hernia repair enables early tissue attachment, reduces adhesions, and could reduce the incidence of recurrences.

Adult↗

A first estimate of ground water ages for the deep aquifer of the Kathmandu Basin, Nepal, using the radioisotope chlorine-36.

The Kathmandu Basin in Nepal contains up to 550 m of Pliocene-Quaternary fluvio-lacustrine sediments which have formed a dual aquifer system. The unconfined sand and gravel aquifer is separated by a clay aquitard, up to 200 m thick, from the deeper, confined aquifer, comprised of Pliocene sand and gravel beds, intercalated with clay, peat, and lignite. The confined aquifer currently provides an important water supply to the central urban area but there are increasing concerns about its sustainability due to overexploitation. A limited number of determinations of the radioisotope 36Cl have been made on bore waters in the basin, allowing us to postulate on the age of ground water in the deeper, confined aquifer. Ground water evolution scenarios based on radioisotope decay, gradual dissolution of formational salts as the ground waters move downgradient, and flow velocity estimations produce comparable ground water ages for the deep waters, ranging from 200,000 to 400,000 years. From these ages, we deduce a mean ground water flow velocity of only 45 mm/year from recharge in the northeast to the main extraction region 15 km to the southwest. We thus estimate current recharge at about 5 to 15 mm/year, contributing 40,000 to 1.2 million m3/year to the ground water system. Current ground water extraction is estimated to be 20 times this amount. The low specific discharge confirms that the resource is being mined, and, based on current projections, reserves will be used up within 100 years.

Chlorine↗

The evolutionary emergence and refinement of the mammalian pattern of foot architecture.

It is shown that in form and function the articular complexes of the monotreme foot are pre-adaptive to the therian condition, but the echidna differs by having a tuber calcaneus which is directed downward and distally. The cynodont foot (TR. 8) and that of the Triassic mammal Eozostrodon seem to possess the essential articular features present in monotremes, but they are assembled rather differently. In both, tuber calcaneus was apparently directed downwards. It follows that monotremes were probably derived from some way along the lineage usually, but inappropriately, termed "Theria'. A calcaneofibular articulation is present in kangaroos, certain shrews, elephant shrews, rabbits and artiodactyls. In all of them it is an apomorphic condition involving annexation of part of the posterior talar facet on the calcaneus by the fibula, which invariably shows some degree of amalgamation with the tibia. It is shown that the trochlear process of the mammalian calcaneus has the dual function of providing origin for the m. flexor accessorius and acting as a supporting shelf for the bundle of peroneal tendons. It is almost certainly a derivative of the lateral flange on the cynodont calcaneus, which presumably had a comparable function. In man, the process is fragmented, one of its derivatives being the lateral process of the calcaneal tuber which shows varying degrees of migration towards the medial process and amalgamation with it. The importance of these morphological features is discussed in relation to their use in cladistic analysis and their relevance to theories of the early evolution of the mammals.

Animals↗

Using in vitro selection to direct the covalent attachment of human immunodeficiency virus type 1 Rev protein to high-affinity RNA ligands.

We have used an in vitro selection procedure called crosslinking SELEX (SELEX = systematic evolution of ligands by exponential enrichment) to identify RNA sequences that bind with high affinity and crosslink to the Rev protein from human immunodeficiency virus type 1 (HIV-1). A randomized RNA library substituted with the photoreactive chromophore 5-iodouracil was irradiated with monochromatic UV light in the presence of Rev. Those sequences with the ability to photocrosslink to Rev were partitioned from the rest of the RNA pool, amplified, and used for the next round of selection. Rounds of photocrosslinking selection were alternated with rounds of selection for RNA sequences with high affinity to Rev. This iterative, dual-selection method yielded RNA molecules with subnanomolar dissociation constants and high efficiency photocrosslinking to Rev. Some of the RNA molecules isolated by this procedure form a stable complex with Rev that is resistant to denaturing gel electrophoresis in the absence of UV irradiation. In vitro selection of nucleic acids by using modified nucleotides allows the isolation of nucleic acid molecules with potentially limitless chemical capacities to covalently attack a target molecule.

Base Sequence↗

Evolution of sentinel lymph node biopsy for melanoma at a National Cancer Institute-designated cancer center.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has rapidly evolved into the standard of care for clinically node-negative melanoma. Since adopting sentinel lymph node (SLN) technology in 1993, we have periodically reviewed our institution's results and made several modifications. METHODS: From January 1993 to December 1998, 182 patients with clinically node-negative primary cutaneous melanoma underwent SLNB. Charts were retrospectively reviewed and assessed for the technique for the identification of the SLN, the pathologic analysis, and the use of intraoperative frozen section. RESULTS: The accuracy of SLN identification improved from 91% to 100% with the combination of isosulfan blue dye and radiolabeled colloid over isosulfan blue dye alone. Routine versus selective lymphoscintigraphy identified 7 in-transit SLNs and increased detection of dual nodal basin drainage (15%-27%). Identification of micrometastases in the SLN increased from 14% to 24% after a modification of pathologic evaluation. The positive SLN was the only involved node in most patients (80%). Intraoperative frozen section had a sensitivity of 58% and was of benefit in only 13 of 124 patients (10%). CONCLUSIONS: Several modifications to the identification of the SLNs and the detection of metastatic melanoma have improved our outcome with SLNB. A careful, periodic review of results to identify areas for improvement at each institution is crucial to the success of SLNB for melanoma.

Adult↗

Time-resolved backbone desolvation and mutational hot spots in folding proteins.

A method is presented to identify hot mutational spots and predict the extent of surface burial at the transition state relative to the native fold in two-state folding proteins. The method is based on ab initio simulations of folding histories in which transitions between coarsely defined conformations and pairwise interactions are dependent on the solvent environments created by the chain. The highly conserved mammalian ubiquitin is adopted as a study case to make predictions. The evolution in time of the chain topology suggests a nucleation process with a critical point signaled by a sudden quenching of structural fluctuations. The occurrence of this nucleus is shown to be concurrent with a sudden escalation in the number of three-body correlations whereby hydrophobic units approach residue pairs engaged in amide-carbonyl hydrogen bonding. These correlations determine a pattern designed to structure the surrounding solvent, protecting intramolecular hydrogen bonds from water attack. Such correlations are shown to be required to stabilize the nucleus, with kinetic consequences for the folding process. Those nuclear residues that adopt the dual role of protecting and being protected while engaged in hydrogen bonds are predicted to be the hottest mutational spots. Some such residues are shown not to retain the same protecting role in the native fold. This kinetic treatment of folding nucleation is independently validated vis-a-vis a Phi-value analysis on chymotrypsin inhibitor 2, a protein for which extensive mutational data exists.

Algorithms↗

Nucleotide excision repair: from E. coli to man.

Nucleotide excision repair is both a 'wide spectrum' DNA repair pathway and the sole system for repairing bulky damages such as UV lesions or benzo[a]pyrene adducts. The mechanisms of nucleotide excision repair are known in considerable detail in Escherichia coli. Similarly, in the past 5 years important advances have been made towards understanding the biochemical mechanisms of excision repair in humans. The overall strategy of the repair is the same in the two species: damage recognition through a multistep mechanism involving a molecular matchmaker and an ATP-dependent unwinding of the damaged duplex; dual incisions at both sides of the lesion by two different nucleases, the 3' incision being followed by the 5'; removal of the damaged oligomer; resynthesis of the repair patch, whose length matches the gap size. Despite these similarities, the two systems are biochemically different and do not even share structural homology. E. coli excinuclease employs three proteins in contrast to 16/17 polypeptides in man; the excised fragment is longer in man: the procaryotic excinuclease is not able by itself to remove the excised oligomer whereas the human enzyme does. Thus, the excinuclease mode of action is well conserved throughout evolution, but not the biochemical tools: this represents a case of evolutionary convergence.

DNA Repair↗

Genetic basis of methicillin resistance in Staphylococcus aureus.

Methicillin resistance in staphylococci is due to the acquisition of the mecA gene encoding a new penicillin-binding protein (PBP2', PBP2a) that has a lower affinity to methicillin than the endogenous PBPs. PBP2' is involved in the assembly of the cell wall peptidoglycan in the presence of high concentrations of beta-lactams that otherwise inhibit the endogenous PBPs. The production of PBP2' is under dual control by its own mecR1-mecI- and the penicillinase blaR1-blaI-encoded regulatory elements. Resistance to high levels of methicillin depends, in addition to PBP2', on chromosomally encoded factors that are involved in the synthesis and degradation of the peptidoglycan. Any mutations that reduce peptidoglycan precursor formation or change the chemical composition of the muropeptide precursor result in lowered resistance.

Evolution, Molecular↗

HIV global surveillance: foundation for retroviral discovery and assay development.

The high level of HIV genetic diversity has important implications for screening, diagnostic testing and patient monitoring. Continued diversification and global redistribution of HIV groups, subtypes and recombinants make it imperative that serological and molecular assays be designed and evaluated to ensure reliable performance on all HIV infections. Recognizing the importance of this issue, we initiated a comprehensive program to monitor global diversification of HIV, search for newly emerging variants, assemble large-volume panels of genetically and geographically diverse strains, and develop strategies to determine the impact of HIV diversity on assays used for detecting and monitoring HIV infection. Efforts to identify and characterize rare and emerging HIV strains have lead to the identification of HIV-1 group O, group N, and dual infections of groups M and O. A panel of plasma specimens was established that includes specimens collected from 12 countries in Africa, Asia, Europe, and South America; the panel comprises infections due to HIV-1 group M subtypes A, B, C, D, F, and G, as well as CRF01, CRF02, and unique recombinant forms, group N, and group O. Serological and molecular characterization of this unique panel has provided vital sequence data to support assay development and an invaluable source of well-defined specimens to evaluate and compare assay performance. The ability to address the challenge posed by ongoing evolution of HIV and the emergence of new variants requires continued surveillance of global HIV strain diversity, a sound scientific foundation for assay development, and suitable panels to evaluate and validate assay performance.

Africa↗

Transpupillary thermotherapy for occult subfoveal neovessels in age-related macular degeneration: importance of patient pigmentation for the determination of laser settings.

BACKGROUND: Presently the indication for transpupillary thermotherapy (TTT) is the treatment of retrofoveal occult subretinal neovascular membranes (OSRNM) for which PDT (photodynamic therapy) has a limited effect. The diode laser power settings given by the manufacturer (Iridex Co, Mountain View, California) have to be modulated according to several criteria including patient pigmentation. The purpose here was to report on a group of patients that presented chorioretinal atrophy after TTT. METHODS: Thirty-eight eyes of 37 patients with OSRNM due to age-related macular degeneration underwent TTT. Indications to treat were diffuse exudative membranes, limited subfoveal OSRNM with a visual acuity of less than 0.4, or a drop of visual acuity of 3 Snellen lines or more since the previous examination. Dual fluorescein and indocyanine green angiography were used for angiographic follow-up. Treatment was performed according to the manufacturer's parameters. The group of patients that presented chorioretinal atrophy after TTT was analysed in this study RESULTS: Five patients presented a limited or spot-size related post-TTT chorioretinal atrophy. Pre-laser visual acuity was 0.34 +/- 0.13 and post-TTT visual acuity was 0.25 +/- 0.15. The OSRNM had disappeared in all cases. The common denominator in these patients was that they were white haired but upon questioning all happened to be dark-haired in their youth. CONCLUSIONS: Evolution towards atrophy can occur after TTT and probably depends on several factors. We showed that pigmentation is a parameter to be evaluated carefully before TTT and that laser power settings should progressively be diminished with increasing patient pigmentation. In white haired persons the original pigmentary status should be part of the patient history.

Aged↗

The redox regulation of intermediary metabolism by a superoxide-aconitase rheostat.

In this article, we discuss a hypothesis to explain the preferential synthesis of the superoxide sensitive form of aconitase in mitochondria and the phenotype observed in manganese superoxide dismutase mutant mice, which show a gross over accumulation of stored fat in liver. The model proposes that intermediary metabolism is redox regulated by mitochondrial superoxide generated during mitochondrial respiration. This regulates the level of reducing equivalents (NADH) entering the electron transport chain (ETC) through the reversible inactivation of mitochondrial aconitase. This control mechanism has a dual function; firstly, it regulates levels of superoxide generated by the ETC and, secondly, it fine-tunes metabolism by channeling citrate either for the production of NADH for energy metabolism or diverting it for the synthesis of fats. In this setting, the mitochondrial redox state influences metabolic decisions via a superoxide-aconitase rheostat.

Aconitate Hydratase↗

MJ0917 in archaeon Methanococcus jannaschii is a novel NADP phosphatase/NAD kinase.

NAD kinase phosphorylates NAD(+) to form NADP(+). Conversely, NADP phosphatase, which has not yet been identified, dephosphorylates NADP(+) to produce NAD(+). Among the NAD kinase homologs, the primary structure of MJ0917 of hyperthermophilic archaeal Methanococcus jannaschii is unique. MJ0917 possesses an NAD kinase homologous region in its C-terminal half and an inositol-1-phosphatase homologous region in its N-terminal half. In this study, MJ0917 was biochemically shown to possess both NAD kinase and phosphatase activities toward NADP(+), NADPH, and fructose 1,6-bisphosphate, but not toward inositol 1-phosphate. With regard to the phosphatase activity, kinetic values indicated that NADP(+) is the preferred substrate and that MJ0917 would function as a novel NADP phosphatase/NAD kinase showing conflicting dual activities, viz. synthesis and degradation of an essential NADP(+). Furthermore, in vitro analysis of MJ0917 showed that, although MJ0917 could supply NADP(+), it prevented excess accumulation of NADP(+); thus, it has the ability to maintain a high NAD(+)/NADP(+) ratio, whereas 5'-AMP would decrease this ratio. The evolutionary process during which MJ0917 arose is also discussed.

Archaeal Proteins↗

The significance of Kleinian contributions to psychoanalysis II. Freudian and Kleinian conceptions of early mental development.

This paper discusses and compares Freudian and Kleinian conceptions of the development of early mental life from the vertices of the genetic hypothesis (and reconstruction), the infantile neurosis, the conception of the evolution of the infant, the issue of reality, and the oedipus complex. In so doing, some of the newer findings of infant development are considered. We can now correlate Kleinian conceptions of early infantile reconstruction in light of these new developments; this paper seeks further to demonstrate that the classical notion of primary narcissism, which is laterally known as the conception of the self-object representation, is incompatible with notions of infantile psychology and therefore leaves the classical conception of early mental life in an ambiguous state. An attempt is made to redress this by reconciling the classical and Kleinian notions via a "dual-tract" theory.

Child Development↗

Multi-membrane-bound structures of Apicomplexa: I. the architecture of the Toxoplasma gondii apicoplast.

Apicomplexan parasites carry a plastid-like organelle termed apicoplast. The previous documentation of four membranes bordering the Toxoplasma gondii apicoplast suggested a secondary endosymbiotic ancestry of this organelle. However, a four-membraned apicoplast wall could not be confirmed for all Apicomplexa including the malarial agents. The latter reportedly possesses a mostly tri-laminar plastid wall but also displays two multi-laminar wall partitions. Since these sectors apparently evolved from regional wall membrane infoldings, the malarial plastid could have lost one secondary wall membrane in the course of evolution. Such wall construction was however not unambiguously resolved. To examine whether the wall of the T. gondii apicoplast is comparably complex, serial ultra-thin sections of tachyzoites were analyzed. This investigation revealed a single pocket-like invagination within a four-laminar wall segment but also disclosed that four individual membranes do not surround the entire T. gondii apicoplast. Instead, this organelle possesses an extensive sector that is bordered by two membranes. Such heterogeneous wall construction could be explained if the inner two membranes of a formerly four-membraned endosymbiont are partially lost. However, our findings are more consistent with an essentially dual-membraned organelle that creates four-laminar wall sectors by expansive infoldings of its interior border. Given this architecture, the T. gondii apicoplast depicts a residual primary plastid not a secondary one as presently proposed.

Animals↗