scholarly journals Current Pharmacologic Approaches for Prevention and Treatment of Bronchopulmonary Dysplasia

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kristen Tropea ◽  
Helen Christou

Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth and has serious adverse long-term health consequences. The etiology of BPD is complex, multifactorial, and incompletely understood. Contributing factors include ventilator-induced lung injury, exposure to toxic oxygen levels, and infection. Several preventive and therapeutic strategies have been developed with variable success. These include lung protective ventilator strategies and pharmacological and nutritional interventions. These strategies target different components and stages of the disease process and they are commonly used in combination. The purpose of this review is to discuss the evidence for current pharmacological interventions and identify future therapeutic modalities that appear promising in the prevention and management of BPD. Continued improved understanding of BPD pathogenesis leads to opportunities for newer preventive approaches. These will need to be evaluated in the setting of current clinical practice in order to assess their efficacy.

2019 ◽  
Vol 36 (S 02) ◽  
pp. S13-S17
Author(s):  
Deepak Jain ◽  
Eduardo Bancalari

AbstractThe evolution of neonatal respiratory support has been one of the cornerstones for the advancements in neonatal–perinatal medicine, allowing survival of infants previously considered not viable. There is an increasing focus on developing strategies which are not only lifesaving but also minimize lung and other organ systems injury, thereby reducing long-term morbidities. Respiratory support immediately after birth is an area that had lagged behind in terms of evidence base and technological advancements until recently. Some of these advancements include use of a respiratory function monitors for measuring flow and tidal volume, new evidence for oxygen supplementation and monitoring, and the efforts to formulate an ideal strategy for establishing functional residual capacity after birth. Increasing evidence for the benefits of avoiding invasive ventilation on reduction of bronchopulmonary dysplasia has resulted in efforts to further reduce the need for endotracheal intubation by applying newer strategies such as less invasive surfactant instillation, noninvasive high-frequency oscillatory ventilation, or use of high flow nasal cannula oxygen. For infants requiring mechanical ventilation, newer strategies such as volume targeted ventilation or neurally adjusted ventilation are being evaluated to reduce ventilator induced lung injury. Despite these advances, there are significant challenges, including lack of conclusive evidence base for many of currently used respiratory strategies, no reduction in the incidence of bronchopulmonary dysplasia in the last decade, and difficulties in defining outcome measures that better reflect long-term respiratory health.


CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.


1996 ◽  
Vol 40 (5) ◽  
pp. 1116-1120 ◽  
Author(s):  
I Walev ◽  
S Bhakdi

An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells were initially damaged by amphotericin B at concentrations of 2.5 to 10 micrograms/ml, as demonstrable by a dramatic drop in cellular K+ levels. Cells could recover from the initial toxic action of the polyene if they were kept in medium of neutral pH, and cellular K+ levels returned to normal after 6 h. However, the recovery mechanisms failed at lower pHs of 5.6 to 6.0. At low pHs, cells became progressively depleted of ATP; they leaked lactate dehydrogenase and became irreversibly damaged after approximately 6 h. The possibility that the low pH characteristic of the distal tubulus lumen renders the renal epithelial cells particularly vulnerable to the toxic action of amphotericin B is raised. The concept is in line with an earlier report that alkalization ameliorates amphotericin B nephrotoxicity in rats.


1997 ◽  
Vol 5 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Robert H Stubbs

Between November 1993 and July 1995, 300 patients underwent penis lengthening surgery. Twelve of these patients had previous genital surgery and/or congenital anomalies, and their procedures could be considered reconstructive. The remaining surgical procedureswere cosmetic. Average patient age was 37 years (range 18 to 74 years). The average preoperative erect length was 12.5 cm (range 7.5 to 16 cm, SD 1.5). ‘Locker room phobia’, adverse female comments and body disproportion were common reasons for patients desiring surgery. All racial groups were represented, with European ancestry the most common. Surgery involved releasing all the superficial (fundiform) ligament and most of the deep suspensory ligament. The defect was filled with plicated gracilis muscle along with shifted skin and subcutaneous tissues. Postoperative traction was used to reduce the chance of scar and penis retraction. The most common major complication was wound infection (5.7%). The most frequent minor problem was dermatitis (13%). Long term (mean10months, range sixto18months) objective measurements using the stretch technique were obtained for 42 patients. One patient lost 1 cm in length, while 41 gained length (mean 3.2 cm, range 0.5 to 6 cm). Poor patient compliance with the postoperative protocol appears to be the most significant factor limiting the success of the procedure.


2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.


2011 ◽  
Vol 52 (9) ◽  
pp. 935-942 ◽  
Author(s):  
Angeliki Dimopoulou ◽  
Hans Raland ◽  
Björn Wikström ◽  
Anders Magnusson

Background Arteriovenous fistulas and grafts are the methods of choice for vascular access in renal failure patients in need of hemodialysis. Their major complication, however, is stenosis, which might lead to thrombosis. Purpose To demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long-term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts (AVF and AVG). Material and Methods During a 17-month period, 31 patients with dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D image postprocessing. Parameters such as comprehension of the anatomy, quality of contrast enhancement, and pathological vascular changes were measured. DSA was then performed in 24 patients. Results MDCTA illustrated the anatomy of the AVF/AVG and the entire vascular tree to the heart, in a detailed and comprehensive manner in 93.5% of the evaluated segments, and depicted pathology of AVF/ AVG or pathology of the associated vasculature. MDCTA demonstrated a total of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24 patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity of 95%. All 24 patients were treated with percutaneous transluminal angioplasty (PTA) with good technical results. Conclusion MDCTA with 3D reconstructions of dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable diagnostic method helping customize future intervention.


Neurosurgery ◽  
1983 ◽  
Vol 12 (4) ◽  
pp. 377-390 ◽  
Author(s):  
Walter Joseph Levy ◽  
Laura Mason ◽  
Joseph F. Hahn

Abstract We reviewed 127 patients who were operated upon for adult presentation Chiari malformation and made six conclusions: (a) The clinical examination remains crucial in the diagnosis. (b) The surgical anatomy is highly varied. (c) Syrinxes can be missed on preoperative contrast studies. (d By a conservative grading system, we determined that 46%; of the patients improved during long term follow-up. One-quarter deteriorated over the long run in spite of any treatment. (e) The overall results did not differ whether the treatment was plugging of the central canal plus decompression or decompression alone. (f) In patients with progression, plugging of the central canal obtained superior results. A review of the literature shows that the natural history of this complex disease process has not been established. This history is needed to identify the course of what may be several important factors that lead to the pathological condition in this disease.


PEDIATRICS ◽  
1986 ◽  
Vol 78 (6) ◽  
pp. 1173-1173
Author(s):  
JEFFREY M. PERLMAN ◽  
JEFF DAWSON

In Reply.— We appreciate the interest in our report published in Pediatrics (1986;77:212-216). The three letters raise similar questions, and in response we would like to make three points. First, including the two infants in the control group who died with the infants in the study group still resulted in significant differences between the two groups regarding duration of furosemide (Lasix) therapy, hypochloremia, or metabolic alkalosis (P > .001). Second (as noted in our discussion), bronchopulmonary dysplasia is a complex disease process.


1986 ◽  
Vol 24 (7) ◽  
pp. 27-28

Dyskinesias are involuntary movements usually of the face and tongue and sometimes of the limbs and trunk. Tardive (delayed) dyskinesia occurs in patients who have been taking an antipsychotic (neuroleptic) drug or, rarely, another central dopamine-receptor-blocking drug such as metoclopramide. It generally occurs only in those treated for longer than a year, although much shorter exposures have been implicated with the antipsychotics. A similar dyskinesia occurred in schizophrenic patients before antipsychotic drugs were introduced, and can occur in healthy untreated elderly people; risk factors include old age, brain damage1 and the schizophrenic disease process.2 Nevertheless, in most patients on an antipsychotic drug (whether psychotic or not), tardive dyskinesia is an unwanted effect of the drug. It occurs in 5–40% of patients on long-term antipsychotic medication.3–5 we discuss here advances in the management of this difficult condition since our last review.6


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