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Pathogenesis of laser-induced choroidal subretinal neovascularization.

The early stages (1 day to 3 weeks) in the development of laser-induced choroidal subretinal neovascularization were studied in the monkey eye. Histopathology revealed that the intense laser beam disrupted the choroid/Bruch's membrane/retinal pigment epithelium (RPE) complex and initiated a repair process. Although all lesions received the same energy density, the initial choroidal wound varied among the lesions: in some, the necrotic choroid was surrounded by hemorrhagic retinal detachment with RPE denudation; in others, the necrotic choroid was surrounded only by minimal damage to the RPE monolayer. Formation of the choroidal wound was followed by an inflammatory response. Later, newly formed choroidal tissue filled the wound and continued to proliferate towards the subretinal space. RPE cells from the edges of the wound proliferated over the newly formed subretinal tissue and closed the wound. In lesions with a large area of damaged RPE, coverage of the wound was slow; fluid accumulated in the subretinal space, and the lesions demonstrated pooling of fluorescein on angiography (leaky lesions). In lesions with minimal damage to RPE monolayer, closure of the wound was rapid, and the proliferating choroidal tissue did not reach the subretinal space. There was no subretinal fluid accumulation and no pooling of fluorescein on angiography (nonleaky lesions). Our results indicate that both the amount of damage of the choroid/Bruch's membrane/RPE complex and the ability of RPE cells around the damaged area to proliferate and restore the continuity of the RPE layer determine the evolution of newly formed choroidal fibrovascular tissue into a subretinal membrane with or without pooling.

Animals↗

[Embryonic development of the teeth].

Embrionary evolution of the tooth in the rat continues four times very clearly. The first of them or "dentair esbozo" it takes place about the 16th day. The second one of them or "caperuza time" between the 17th and 18th day. The third one of them or "bell time" it takes place 19th, 20th and 21th days. At the end the fourth one of then or "of resolution" it takes place the 22 and first of the afterborn days.

Animals↗

Fine mapping of chromosome 22 breakpoints within the breakpoint cluster region (bcr) implies a role for bcr exon 3 in determining disease duration in chronic myeloid leukemia.

The chromosomal translocation that fuses the phl gene with the c-abl proto-oncogene appears to be a pivotal step in the pathogenesis of some leukemias. In chronic myeloid leukemia (CML) the breakage within the phl gene is largely confined to a 5.8-kb segment referred to as the breakpoint cluster region (bcr). To determine whether the presence of specific bcr exons on the Philadelphia chromosome has any clinical significance, we have analyzed the bcr breakpoints in 134 patients with CML. As many as five probes were used in this analysis, including a synthetic oligonucleotide probe homologous to the bcr exon 3 (phl exon 14) region. The distribution of breakpoints indicates that, in fact, breakage is largely confined to a 3.1-kb segment lying between bcr exon 2 and exon 4 (phl exons 13-15). In 61 CML patients analyzed within 1 year of diagnosis, the distribution of breakpoints appeared to be random within the 3.1-kb region. However, a significant excess of 5' breakpoints was observed in the total population studied, consistent with previous data showing that patients with 3' breakpoints have shorter disease durations. Analysis using the bcr exon 3 sequence probe indicated it was probably the presence or absence of bcr exon 3 on the Philadelphia chromosome that accounts for some of the variability in disease duration seen in CML. The data suggest that the phl/abl protein product may influence the timing of the onset of blast crisis and imply a continuing role for this protein during the evolution of the disease.

Blotting, Southern↗

Influence of hyposensitization with Dermatophagoides pteronyssinus extract on clinical score, total and specific IgE levels, and skin test in asthmatic patients.

To evaluate the effects of immunotherapy on clinical response, on IgE serum level, on radioallergosorbent test (RAST), and on skin tests, a prospective study was performed by a follow-up of 73 asthmatic patients allergic for house dust during hyposensitization with Dermatophagoides pteronyssinus extract. No relationship could be found between the evolution of clinical score, skin tests and RAST, but 91% of the patients with a decreasing IgE serum level had satisfactory clinical results. Serial determinations of serum IgE levels during hyposensitization showed two patterns of evolution with a favourable prognostic value: a continuously decreasing serum IgE or a primary increase followed by a late decrease.

Allergens↗

[Evaluation of mechanical ventilation in meconial aspiration syndrome].

Twenty seven newborn with serious meconial aspiration syndrome are studied. Two groups are stablish weather they require or not mechanical ventilation during evolution. When comparing various perinatal and clinical data, only the Silverman test showed statistically significant differences; pH and gases in blood during the first hours of life did not showed differences. Pneumothorax incidency in both groups was 33%. Twelve newborn required mechanical ventilation. The starting age was 24 hours of life range 3-54 hours. Most frequent indication was hipoxemia and apnea. Use of intermitent positive pressure improved PaCO2 with a light increase in PaO2 though it also increased alveolo-arterial oxygen gradient. Hipoxemia was the most relevant data in evolution of these patients. In seven cases continuous distending pressure was applied, with a light increase in PaO2 only in three patients. No patient suffered pneumothorax during mechanical ventilation. In patients with mechanical ventilation mortality was 25%. The possibility of an addition in certain cases of pulmonary hypertension with right-to-left shunting ductal and atrial is reported.

Age Factors↗

[Arterial hypertension in Spain].

This paper is the written version of the conference that under the same title was presented in the XXX Congreso Nacional de la Sociedad Española de Cardiología. In the paper, the topic of arterial hypertension (AHT) in Spain is approached from different perspectives, as well as to what extend cardiologists influence or are influenced by it. First, there is a brief overview concerning the diagnostic and therapeutic status of AHT in the population, and its evolution in the last years. The paper continues analyzing the research on AHT sponsored by the Fondo de Investigación Sanitaria in recent years, and emphasizes the little participation of cardiologists as principal investigators in this area. Next, publications in Spanish and international scientific journals are assessed. To end the paper, a proposal of the possible role of the cardiologist on diagnosis, treatment, continued education and research on hypertension is presented.

Adult↗

Variety and evolution of American endoscopic image management and recording systems.

The rapid evolution of computing technology has and will continue to alter the practice of gastroenterology and gastrointestinal endoscopy. Development of communication standards for text, images, and security systems will be necessary for medicine to take advantage of high-speed computing and communications. Professional societies can have an important role in guiding the development process.

Computer Communication Networks↗

[New frontiers in myocardial preservation].

The high hospital mortality due to primary graft failure, together with the ever more frequent use of "Suboptimum" donors because of the scarcity of organs has, in the recent years, caused renewed interest in perfectioning techniques of cardiac preservation. The numerous studies supporting the benefits of a period of controlled warm reperfusion after global ischemia, and the growth of the continuous warm blood cardioplegia, led us to the evolution of our own technique for myocardial protection during transplantation. Dr John Wallwork introduced the concept of donor "resuscitation" in the attempt to improve the hemodynamic state of the donor, by preload and afterload manipulation and pharmacological treatment of the unstable or "marginal" donor. The Juan Canalejo Hospital introduced the concept "Resuscitation during the implantation" using continuous warm blood cardioplegia. Maintenance of normothermia during heart transplantation produces what is referred to as "cell repair" or "resuscitation during the implantation" and avoid the reperfusion damage. From january 1992 to april 1995, 91 orthotopic heart transplantation were performed at our institution. By harvesting we have employed the conventional preservation technique. We performed a controlled continuous anterograde/retrograde warm blood cardioplegic reperfusion of the graft, before and during the implantation in 53 patients. Since january 1994 we performed in 38 cases the same controlled continuous warm blood reperfusion, but only anterograde. Continuous warm blood cardioplegia in heart transplantation is a safety myocardial protection method. Trasplant programs require the optimal use of the available donors.

Heart↗

[Serologic study in patients with streptococcal infective endocarditis].

BACKGROUND: Infective endocarditis is a systemic disease in which there are a continuously antigenic stimulation of immunologic system. Streptococcus is still the most frequent cause of infective endocarditis. PATIENTS AND METHODS: We investigated the presence of antibody (AB), total and IgM by indirect immune fluorescence technique, in four groups of population: streptococcal infective endocarditis (SIE), streptococcal bacteraemia (SB), Staphylococcus aureus endocarditis, and healthy people. Antigens used were: 1) their own strain isolated from the blood of patients with SIE and SB ¿homologous AB¿, and; 2) seven species of Streptococcus: Streptococcus intermedius, Streptococcus salivarius, Streptococcus bovis, Streptococcus sanguis I, Streptococcus sanguis II, nutritional dependent streptococci and Enterococcus faecalis (heterologous AB). RESULTS: Homologous antibodies: titers > or = 1/512 were found in all patients with SIE and only in 2 with SB (sensitivity 100% and specificity 93%). IgM titer (threshold 1/32) was positive only in patients with SIE (sensitivity 75,5% and specificity 100%). The fall of the AB titer was continuous and slow, despite the good clinical evolution of patients. (AB titers were > or = 1/512 and IgM > or = 1/64 in 30% of patients 1 year later). Heterologous AB: in spite of statistically significant difference found in SIE versus the other groups, sensitivity of this test (threshold 1/256) is low, confidence interval include expected random value (50%), specificity is 88%. CONCLUSIONS: The utility of homologous AB for diagnosing infective endocarditis is demonstrated. On the contrary for heterologous AB, antigenic common fractions must be found in the different species.

Adult↗

The "presyrinx" state: a reversible myelopathic condition that may precede syringomyelia.

BACKGROUND AND PURPOSE: Alteration of CSF flow has been proposed to be an important mechanism leading to the development of syringomyelia. We hypothesize that a "presyrinx" condition attributable to a potentially reversible alteration in normal CSF flow exists and that its appearance may be caused by variations in the competence of the central canal of the spinal cord. METHODS: Five patients with clinical evidence of myelopathy, no history of spinal cord trauma, enlargement of the cervical spinal cord with T1 and T2 prolongation but no cavitation, evidence of altered or obstructed CSF flow, and no evidence of intramedullary tumor or a spinal vascular event underwent MR imaging before and after intervention that alleviated obstruction to CSF flow. RESULTS: Preoperatively, all patients had enlarged spinal cords and parenchymal T1 and T2 prolongation without cavitation. Results of MR examinations after intervention showed resolution of cord enlargement and normalization or improvement of cord signal abnormalities. In one patient with severe arachnoid adhesions who initially improved after decompression, late evolution into syringomyelia occurred in association with continued CSF obstruction. CONCLUSION: Nontraumatic obstruction of the CSF pathways in the spine may result in spinal cord parenchymal T2 prolongation that is reversible after restoration of patency of CSF pathways. We refer to this MR appearance as the "presyrinx" state and stress the importance of timely intervention to limit progression to syringomyelia.

Adult↗

2,500-year evolution of the term epidemic.

The term epidemic (from the Greek epi [on] plus demos [people]), first used by Homer, took its medical meaning when Hippocrates used it as the title of one of his famous treatises. At that time, epidemic was the name given to a collection of clinical syndromes, such as coughs or diarrheas, occurring and propagating in a given period at a given location. Over centuries, the form and meaning of the term have changed. Successive epidemics of plague in the Middle Ages contributed to the definition of an epidemic as the propagation of a single, well-defined disease. The meaning of the term continued to evolve in the 19th-century era of microbiology. Its most recent semantic evolution dates from the last quarter of the 20th century, and this evolution is likely to continue in the future.

Disease Outbreaks↗

Chest wall disruption with and without acute lung injury: effects of continuous positive airway pressure therapy on ventilation and perfusion relationships.

OBJECTIVE: We investigated the evolution of lung injury in an animal model with multiple rib fractures, both with and without acute lung injury, and the influence of spontaneous breathing with continuous positive airway pressure (CPAP) therapy on the relative distributions of alveolar ventilation ([OV0312]a) and perfusion ([OV0422]). DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of ventilation/perfusion distribution, pulmonary mechanics and gas exchange, and cardiovascular variables. SETTING: University experimental research laboratory. SUBJECTS: Twenty-nine domestic swine. INTERVENTIONS: Anesthetized pigs were assigned randomly to undergo chest wall dissection alone or chest wall dissection and bilateral fractures of ribs with or without oleic acid-induced acute lung injury. MEASUREMENTS AND MAIN RESULTS: Gas exchange was evaluated by blood gas analysis and multiple inert gas elimination technique. After baseline data were collected, subsequent data were collected at 60 and 120 mins after experimental injuries, and at 180 mins, which was 60 mins after titration of CPAP therapy. The range of CPAP was 4-22 cm H2O. Shunt ([OV0312]a/[OV0422] < 0.005), venous admixture [OV0312]a/[OV0422] < 0.1), and functional deadspace ([OV0312]a/[OV0422] > 10) before injury were similar among all animals and ranged from 3.4% to 4.5%, 4.2% to 5.0%, and 54.4% to 56.5%, respectively. There were no changes, throughout the study, in lung regions with low [OV0312]a/[OV0422] (0.005 < [OV0312]a/[OV0422] </= 0.1) in any group of animals. Shunt of control animals increased to 10.5 +/- 8.8% (p <.05) at 60 mins but demonstrated no further changes in [OV0312]a/[OV0422] at subsequent measurements. Shunt also increased after animals underwent bilateral rib fractures without (12.7%, p <.05) and with (19.9%, p <.05) acute lung injury; however, it decreased in both groups after the application of CPAP (4.6% and 6.6%, respectively, p <.05). All changes in venous admixture directly reflected the change in shunt at all intervals. Functional deadspace was unaffected by chest wall dissection, rib fractures, or subsequent lung injury but decreased after CPAP therapy in all animals. CONCLUSIONS: Acute lung injury exacerbated the right-to-left intrapulmonary shunt seen within the first hour after disruption of the chest wall. Application of CPAP decreased shunt, improved matching of [OV0312]a/[OV0422], and reduced the requirement for supplemental oxygen, without any significant impairment in cardiovascular function.

Analysis of Variance↗

The evolution of kinship care policy and practice.

Kin caregivers can provide continuity and connectedness for children who cannot remain with their parents. This is one reason kinship care has become the preferred placement option for foster children. However, despite the growing reliance on kin caregivers, kinship care policies have evolved with little coherent guidance. This article examines kinship care and finds: Kinship foster parents tend to be older and have lower incomes, poorer health, and less education than non-kin foster parents. As a result, kin caregivers face more challenges as foster parents than non-kin caregivers. The links between payment and licensure, and the haphazard evolution of licensing policies and practices, complicate efforts to provide fair compensation for kin caregivers. Kinship caregivers receive less supervision and fewer services than non-kin caregivers, thus kin may not receive the support they need to nurture and protect the children in their care, even though their needs for support may be greater. Kinship foster care questions many traditional notions about family obligation, governmental responsibility, and the nature of permanency for children in care. The article concludes by discussing these concerns, and calls for more thoughtful consideration of the uniqueness of kinship care in developing policies and best practices.

Adoption↗

Evolutionary and functional analysis of the tailless enhancer in Musca domestica and Drosophila melanogaster.

To further understand the evolutionary dynamics of the regulatory interactions underlying development, we expand on our previous analysis of hunchback and compare the structure and function of the tailless enhancer between Musca domestica and Drosophila melanogaster. Our analysis shows that although the expression patterns and functional protein domains of tll are conserved between Musca and Drosophila, the enhancer sequences are unalignable. Upon closer investigation, we find that these highly diverged enhancer sequences encode the same regulatory information necessary for Bicoid, Dorsal, and the terminal system to drive tll expression. The binding sites for these transcription factors differ in the sequence, number, spacing, and position between the Drosophila and Musca tll enhancers, and we were unable to establish homology between binding sites from each species. This implies that the Musca and Drosophila Bcd-binding sites have evolved de novo in the 100 million years since these species diverged. However, in transgenic Drosophila embryos the Musca tll enhancer is able to drive the same expression pattern as endogenous Drosophila tll. Therefore, during the rapid evolution of enhancer sequences individual binding sites are continually lost and gained, but the transcriptional output is maintained by compensatory mutations in cis and in trans.

Amino Acid Sequence↗

Directed evolution strategies for improved enzymatic performance.

The engineering of enzymes with altered activity, specificity and stability, using directed evolution techniques that mimic evolution on a laboratory timescale, is now well established. However, the general acceptance of these methods as a route to new biocatalysts for organic synthesis requires further improvement of the methods for both ease-of-use and also for obtaining more significant changes in enzyme properties than is currently possible. Recent advances in library design, and methods of random mutagenesis, combined with new screening and selection tools, continue to push forward the potential of directed evolution. For example, protein engineers are now beginning to apply the vast body of knowledge and understanding of protein structure and function, to the design of focussed directed evolution libraries, with striking results compared to the previously favoured random mutagenesis and recombination of entire genes. Significant progress in computational design techniques which mimic the experimental process of library screening is also now enabling searches of much greater regions of sequence-space for those catalytic reactions that are broadly understood and, therefore, possible to model. Biocatalysis for organic synthesis frequently makes use of whole-cells, in addition to isolated enzymes, either for a single reaction or for transformations via entire metabolic pathways. As many new whole-cell biocatalysts are being developed by metabolic engineering, the potential of directed evolution to improve these initial designs is also beginning to be realised.

Journal Article↗

A time for reflection: providers rethink plan ownership.

Even as recently as a year ago, the buzz in the healthcare provider community continued to be largely positive regarding the development and evolution of provider-sponsored health plans. But recent market shifts and setbacks are forcing a rethinking of the provider-sponsored plan concept. While a small number of such plans in various markets across the U.S. continue to do well, many others are floundering, being sold, or closed down outright. In this article, provider-sponsored plan executives discuss their experiences, and they and industry observers approach questions of whether miscalculations have taken place and continue to take place in this rapidly changing arena of peril and opportunity. In particular, much attention has focused on Medicare provider-sponsored organization (PSO) development under the Balanced Budget Act. But, as industry observers and executives agree, the issues around all kinds of provider-sponsored managed care are now on the table for discussion as never before.

Decision Making↗