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Biomedical subjects

R F Wilson

Publications and source records attributed to R F Wilson.

At least 361 records · Page 20Linked to original sources
PubMedDate not supplied

Colchicine encapsulation within poly(ethylene glycol)-coated poly(lactic acid)/poly(epsilon-caprolactone) microspheres-controlled release studies.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses have the potential to prevent restenosis. However, the development of injectable microspheres for maintaining high tissue levels of drugs at the site of vascular injury is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, colchicine, in polyethylene glycol (PEG)-coated biodegradable microspheres composed of poly(lactic acid)/poly(epsilon-caprolactone) blends, with a mean diameter of 3-6 microm. A solution of colchicine and blends of polylactic acid (PLA)/polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol) with stirring by a high-speed homogenizer to form microspheres. Colchicine recovery in microspheres ranged from 30-50% depending on the emulsification system and the ratio of polymer blends used for the preparations. Scanning electron microscopy revealed that the PLA/PCL microspheres were spherical in shape and had a smooth surface texture. Results of in vitro release studies showed that it is possible to control the colchicine release by choosing the appropriate particle size, loading, and PLA/PCL composition. Water permeability through the PLA membrane was greater, when compared with PCL blends. The amount of drug release also was much higher (58.3%) in PLA compared with PCL (39.3%) microspheres, for 30 days. Therefore, we concluded that the drug release from the microspheres followed a diffusion mechanism where bulk erosion and surface deposition were negligible. These PEG-coated PLA/PCL microspheres may have potential for targeting antiproliferative agents for prolonged periods to treat restenosis.

Caproates↗
PubMedDate not supplied

Development of poly(Lactic acid)/chitosan co-matrix microspheres: controlled release of taxol-heparin for preventing restenosis.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Controlled release of appropriate drugs alone and in combinations is one approach for treating coronary obstructions, balloon angioplasty, restenosis associated with thrombosis, and calcification. We demonstrated the possibility of encapsulating taxol-loaded polylactic acid (PLA) microspheres within heparin-chitosan spheres to develop a prolonged release co-matrix form. The in vitro release profile of taxol and heparin from this co-matrix system was monitored in phosphate buffered saline pH 7.4, using an ultraviolet spectrophotometer. The amount of taxol/heparin release was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release of taxol (15.8%) and heparin (32.7%) from the co-matrix was modified with polyethylene glycol coatings (13.5% and 25.4%, respectively, for 24 hr). From scanning electron microscopy studies, it appears that these drugs diffuse out slowly to the dissolution medium through the micropores of the co-matrix. However, the surface micropores were modified with polyethylene glycol (PEG) coatings for a constant slow release profile. This PEG-coated PLA/chitosan co-matrix may target drug combinations having synergestic effects for prolonged periods to treat restenosis.

Anticoagulants↗
PubMedDate not supplied

Acute respiratory failure.

There appears to be a great similarity between all of the various types of Adult Respiratory Distress Syndromes (ARDS) in that they are all characterized by progressively increasing interstitial edema in the lungs and a reduced functional residual capacity. Early diagnosis is mandatory and therapy should be started as soon as there is a reasonable suspicion, based on the patient's injury or illness and the previous condition of his lungs, that acute respiratory failure is developing. Sepsis, shock, CNS or thoracic disease and trauma are important associated factors. Blood gas changes usually cannot be appreciated clinically until the respiratory problem is quite severe. Accordingly, serial blood gas analyses should be performed on any patient who has a reasonable chance of developing ARDS. We have found that changes in the estimated AaDO2 on room air are especially helpful. Any deterioration in the patient's clinical condition, blood gases or ventilatory effort should be considered as an indication for early ventilatory assistance. Control of the primary process, careful dehydration, high tidal volumes, and PEEP are the mainstays of therapy. Serial blood gases and careful observation of the patient's effective compliance are essential to determine the optimal ventilator setting and the optimal amount of PEEP. Recently intermittent mandatory ventilation (IMV) with very large amounts of PEEP have been reported to be of value. Early administration of massive steroids should be considered if the patient fails to respond promptly to correction of the underlying etiologic problem, particularly sepsis, careful progressive dehydration and optimal expansion of the alveoli, with high tidal volumes and PEEP.

Acute Disease↗
PubMedDate not supplied

Management of patients with head injuries and multiple other trauma.

The management of patients with multiple trauma including head injuries is a complex task. The prime goal is to minimize secondary neuronal injury. Attention to establishment of an airway, assurance of adequate gas exchange, and circulatory resuscitation is mandatory to minimize any secondary neuronal injuries. Once these principles of resuscitation have been applied and the primary neuronal injury is treated, additional etiologies of secondary brain trauma, such as hypoglycemia and hypothermia, should be addressed. Continual monitoring of oxygenation and perfusion is mandatory optimizing the outcome of these patients.

Craniocerebral Trauma↗
PubMedDate not supplied

The nutritional management of patients with head injuries.

Severe head injuries tend to be associated with hypermetabolism and hypercatabolism resulting in negative nitrogen balances which may exceed 30 grams day-1. Enteral feeding should begin as soon as the patient is hemodynamically stable, attempting to reach a non-protein caloric intake of at least 30-35 kcal kg-1 day-1 and a protein intake of 2.0-2.5 g kg-1 day-1 as soon as possible. With severe head injuries (Glasgow Coma Scale < 8), there is an increased tendency for gastric feeding to regurgitate into the upper airway. Keeping the patient upright and checking residuals is important in such patients. Jejunal feedings are less apt to be aspirated. If it is apparent that the gastro-intestinal tract cannot be used to reach the nutritional goals within three days, total parental nutrition is begun within 24-48 h so as to reach these nutrition goals by either one or both routes by the third or fourth day. Blood glucose levels exceeding 150-200 mg dl-1 tend to increase the severity of the neurologic problems and efforts should be made to prevent hyperglycemia by carefully regulating the glucose and insulin intake. Indirect calorimetry to determine the respiratory quotient and resting energy expenditure should be determined twice weekly. To determine N2 balance, urinary urea nitrogen should be measured in 24-h specimens. These tests should be performed once or twice weekly until it is clear that the nutrition is adequate.

Craniocerebral Trauma↗
PubMedDate not supplied

The diagnosis and management of severe sepsis and septic shock.

Shock due to or associated with sepsis may present a clinical picture quite different from that usually seen in hypovolemic or cardiogenic shock. Any trend which suggests increasing sepsis should be treated aggressively as if shock were present. The earlier such therapy is begun, the better the results tend to be. Perhaps the greatest errors in the therapy of severe sepsis and septic shock are (1) delayed control of the primary septic process, (2) giving too little fluid in the early phases of therapy (and too much later), and (3) delaying ventilator assistance if the patient's ventilation or blood gases are deteriorating.

Acid-Base Equilibrium↗
PubMedDate not supplied

The diagnosis and treatment of acute respiratory failure in sepsis.

Early diagnosis is mandatory in the adult respiratory distress syndromes, particularly in sepsis, and therapy should begin as soon as there is a reasonable suspicion that this problem is developing. Blood-gas changes cannot usually be appreciated clinically until the respiratory problem is quite severe. Accordingly, serial blood-gas analyses should be performed in any septic patient who has an increased chance of developing ARDS. Any deterioration in the patient's condition, blood gases, or ventilatory effort should be considered as an indication for early ventilatory assistance. Control of the primary process, high tidal volumes, PEEP, and careful dehydration are the mainstays of therapy. Serial blood gases and careful observation of the patient's effective compliance are essential to determine the optimal ventilator settings and the optimal PEEP. Early administration of massive steroids should be considered if the patient fails to respond to correction of the underlying etiologic problem (particularly sepsis), careful progressive dehydration, and optimal expansion of the alveoli (using high tidal volumes and/or PEEP).

Blood Gas Analysis↗
PubMedDate not supplied

Effects of 10-hydroxycamptothecin, delivered from locally injectable poly(lactide-co-glycolide) microspheres, in a murine human oral squamous cell carcinoma regression model.

This study investigated whether local delivery of 10-hydroxycamptothecin provides effective inductive chemotherapy as assessed by significant tumor reduction. Established tumorigenic human oral squamous cell carcinoma cells were used for these experiments. The experimental groups were comprised of: control (blank (no drug) poly(lactide-co-glycolide) (PLGA) microspheres), intraperitoneal 10-hydroxycamptothecin delivery + blank microspheres, local bolus 10-hydroxycamptothecin + blank microspheres, and PLGA controlled-release microspheres. The 10-hydroxycamptothecin dose administered was 12 mg/kg (bolus-intraperitoneal, local) or controlled-release over 10 days. Regardless of delivery route, 10-hydroxycamptothecin significantly reduces tumor volume. However, PLGA microspheres provide significantly higher intratumor-drug concentrations (approximately 10 and 100 fold higher) relative to local bolus and intraperitoneal routes, respectively. Also, only the PLGA microspheres significantly reduced tumor weights. Camptothecin clinical applications are limited by drug inactivation at physiological pH and the need for sustained infusions. However, due to their acidic, camptothecin-stabilizing microclimate, PLGA microspheres could provide a novel delivery system for camptothecin-based induction chemotherapy.

Animals↗
PubMedDate not supplied

Endocrine changes in sepsis.

The hormonal changes associated with sepsis appear to be important compensatory responses directed toward (1) increasing the availability of fuel (glucose, fatty acids, and amino acids) for the greatly accelerated needs of the cellular metabolic machinery and (2) maintaining an adequate blood volume, blood pressure, and tissue perfusion. Unrecognized or inadequately treated sepsis with subsequent prolonged trophic hormone stimulation depletes the patient of fuels necessary for the maintenance of the increased metabolic demands. This leads to eventual deleterious effects with muscle wasting, increased susceptibility to infection, and impaired wound healing. Manipulation of some of the hormones in sepsis, particularly insulin, glucagon, and growth hormone, with an adequate caloric intake to promote a more favorable anabolic response, holds exciting promise.

Adrenal Cortex↗