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Biomedical subjects

K Davenport

Publications and source records attributed to K Davenport.

At least 19 recordsLinked to original sources

Evidence for the use of silver-alloy-coated urethral catheters.

Catheter-associated urinary tract infections (CAUTIs) are a common occurrence and are associated with increased patient morbidity and mortality. In addition, they delay patient discharge from hospital, substantially increase hospital costs and promote the emergence of resistant organisms. Any intervention resulting in a decrease in the incidence of CAUTIs would have a significant impact on patient quality of life and hospital costs. By reviewing the current literature, it can be seen that the use of silver-alloy-coated hydrogel catheters can reduce CAUTIs by up to 45%. Despite reducing CAUTIs in most hospital situations, the greatest reduction is seen in postoperative patients, intensive care unit patients and burns patients.

Alloys↗

MAP kinase pathways in the yeast Saccharomyces cerevisiae.

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Calcium-Calmodulin-Dependent Protein Kinases↗

Propylene glycol-induced proximal renal tubular cell injury.

Propylene glycol is a solvent that is used in many oral, injectable, and topical medications. Although uncommon, acute renal failure has been attributed to propylene glycol. The mechanism of propylene glycol-mediated renal injury is unknown. We report a case of acute renal failure in a 16-year-old boy given large doses of pentobarbital and phenobarbital, both of which are solubilized with propylene glycol. A renal biopsy showed proximal renal tubular cell swelling and vacuole formation. The data from this case suggest that the reversible acute renal failure caused by propylene glycol is attributable to proximal renal tubular cell injury.

Acute Kidney Injury↗

The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin.

The objective of this study was to investigate the effects of intravenous erythromycin and chronic oral dosing of erythromycin on gastric emptying in patients with idiopathic or diabetic gastroparesis. Symptoms were assessed on oral dosing and during long-term follow-up in an ambulatory setting at a University referral center. Fourteen patients (10 idiopathic and four diabetic gastroparesis) were studied. Four patients left during the 4-wk study; two due to rash, one with cramps and vomiting on erythromycin, and one due to other medical problems. Ten patients completed the 4-wk study and commenced long-term therapy. Five of these patients experienced enough symptomatic relief to continue oral erythromycin long-term, being followed for an average period of 8.4 months. After initial documentation of delayed gastric emptying, patients received 6 mg/kg intravenous erythromycin lactobionate before a second gastric emptying study. Erythromycin base was then given orally at a dose of 500 mg tid-ac and qhs, with a final gastric emptying study performed after 4 wk. During long-term follow-up, erythromycin dosage was adjusted to minimize symptoms. Radionuclide-labeled gastric emptying of a solid meal was studied at baseline, following intravenous erythromycin, and after 4 wk of oral treatment with erythromycin. Symptom scores were assessed at baseline, at 4 wk, and then at 8-wk intervals. The percentage of the solid meal retained in the stomach at 2 h decreased from 85% +/- 11% (SD) at baseline to 20% +/- 29% following intravenous erythromycin (p < 0.001), and to 48% +/- 21% after 4 wk of oral therapy (p < 0.01 vs. baseline). There was a reduction in total symptom scores and a significant reduction in global assessment scores (p = 0.03). We conclude that erythromycin has a strong gastric prokinetic effect in both idiopathic and diabetic gastroparesis, and may represent a useful new therapeutic approach to this problem.

Administration, Oral↗

The laser Doppler analysis of posturally induced changes in skin blood flow at elevated temperatures.

Recently, it has become possible to use laser Doppler techniques to separately quantitate the two components of blood flow, microvascular volume and red blood cell velocity. We used these techniques in 21 normal volunteers to quantitate the effect of postural changes in skin blood flow and its components at 35 degrees C and at 44 degrees C. Postural skin blood flow changes have ben studied extensively at basal skin temperature, but not at elevated temperatures. We contrasted changes at sites with arteriovenous anastomotic (AVA) blood flow (toe and finger pulps) with changes at sites with primarily nutritive flow (elbow and knee). Skin blood flow increased markedly with increasing temperature. The increases at the elbow and knee were the products of equivalent increases in both microvascular volume and velocity. In contrast, the increases on the finger and toe pulps were mainly due to increases in velocity. Elevation of both upper and lower extremities brought about a decrease in skin blood flow. Dependency increased blood flow. The magnitudes of observed changes were greater on the lower extremity than on the upper extremity and greater at 44 degrees C than at 35 degrees C. Once again, with postural change, the nutritive areas exhibited similar changes in volume and velocity while the AVA areas primarily showed velocity alterations. The correlation of systolic pulse pressures with blood flow was greater at the AVA areas than at nutritive areas and greater at 44 degrees C than at 35 degrees C. This correlation was with the velocity rather than with the volume component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of acutely infected arthroplasty with local antibiotics.

The authors have identified 22 patients with acutely infected total joint arthroplasties, 9 hips, and 13 knees. Following organism identification and assessment of the patients' general medical condition, the patients were treated with an implantable antibiotic pump. This allowed the delivery of a high concentration of antibiotic solution to a localized area. Systemic levels of antibiotic were kept to a minimum, thereby eliminating potential serious side effects of antibiotic treatment. Local concentrations were extremely high, exceeding the minimal inhibitory concentration (MIC) in all cases by 8-10-fold. Twenty patients have been followed for 30 months, and of these, 17 patients are considered to be infection free. There were three failures. The organisms that have been treated have been gram negatives, gram positives, and some mixed infections. Results are encouraging with this form of treatment, and additional patients are continually being added to the study.

Amikacin↗

Extrathoracic and transthoracic management of vascular disease of the aortic arch branches: a 16-year experience.

To determine factors influencing results of operation for proximal brachiocephalic arterial disease, a 16-year review of 74 consecutive patients was undertaken. A total of 62 subclavian, 14 common carotid, 6 innominate, and 2 vertebral arteries were revascularized during 79 procedures. The approach was transthoracic in 12 operations and extrathoracic in 67. Mean follow-up was 57 +/- 45 months. Two patients (2.5%) died of stroke after extrathoracic revascularization of the common carotid artery. Cumulative 5-year and 10-year freedom from neurological events was 81% and 75%, respectively. The best results were obtained with transthoracic procedures, with revascularization of the subclavian artery rather than the common carotid artery, and in operations performed in patients without associated distal carotid disease. In view of the recent progress in operative techniques and postoperative surgical care, the choice between the transthoracic approach and the extrathoracic approach should not be biased; rather, they should remain equal and viable alternatives based on anatomical and clinical features of the individual patients.

Adult↗

Operative treatment of displaced intra-articular fractures of the calcaneus.

Thirty-five patients with 41 calcaneus fractures, seen at Cook County Hospital over a 3 1/2-year period, underwent an open reduction and internal fixation of their fractures through a sinus tarsi incision. Bohler's angle averaged 6 degrees preoperatively and 26 degrees postoperatively. An additional measurement, the critical angle, was defined. This angle is a measurement of the congruency of the posterior facet. It facilitated the selection of patients for an open reduction as well as allowed a determination of the adequacy of restoration of the joint surfaces postoperatively. In this series the critical angle averaged 26 degrees preoperatively and 1 degree postoperatively. Followup was possible in 73% of the patients. Almost all of the patients exhibited some degree of limitation of motion of the subtalar joint, but the reduction of the fracture fragments was maintained in all cases and secondary deformity and complaints did not develop.

Adult↗

Local delivery of antibiotics via an implantable pump in the treatment of osteomyelitis.

Twenty-one patients with osteomyelitis were treated with surgical debridement and local antibiotic therapy. Amikacin (19 patients) or netilmicin (2 patients) was delivered locally via a pump implanted subcutaneously. The outflow catheters were led from the pump subcutaneously to the infected area and placed in the defect created by the surgical debridement. The pump was refilled at intervals, on an outpatient basis. The pump was surgically removed at the conclusion of therapy. Follow-up evaluation was for 12-27 months. The duration of hospitalization was five to 52 days (mean, 23 days). The infusions were sustained for 32-140 days (mean, 63 days). Systemic levels of antibiotics were always below acceptable trough levels. Levels in the wound drainage of the 11 patients who drained after operation were always greater than the upper limit of the assay. Nephrotoxicity and ototoxicity were determined using pre- and posttherapy creatinine clearances and audiograms. Two patients exhibited minimal nephrotoxicity (creatinine clearance of 66 ml/minute and 55 ml/minute; normal, 70 ml/minute). There were no other adverse effects of the antibiotics. Sixteen patients have not drained since removal of the pumps.

Adult↗

GU-PACU orientation.

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Ambulatory Surgical Procedures↗

Antibiotics delivered by an implantable drug pump. A new application for treating osteomyelitis.

Osteomyelitis is usually treated with wide surgical debridement and prolonged intravenous antibiotics. The advent of the implantable drug pump has led us to evaluate this therapeutic modality for the treatment of osteomyelitis. We have previously shown that amikacin retains microbiologic activity in an implantable drug pump over a six-week period when incubated at 37 degrees C. We have also demonstrated in rabbits that high local levels and low systemic levels of antibiotic can be achieved using an implantable drug pump as a delivery system and that this method can be used to sterilize infected wounds. This method was applied in the treatment of osteomyelitis in 14 patients whose duration of symptoms ranged from one month to 22 years. In 13 patients, active drainage had been present for more than six months, and all patients had undergone one or more attempts at eradication of their infection. Prior therapy included surgical debridement alone (one patient), one or more attempts at debridement and extended intravenous antibiotic therapy (13 patients), debridement and local flap procedures (four patients), and extended oral antibiotic therapy (two patients). The bones involved were the tibia (six patients), femur (four patients), and elbow, shoulder, hip, and radius (one patient each). Intra-operative cultures indicated that the infecting organism was Staphylococcus aureus alone (seven patients), S. aureus in combination with gram-negative bacteria (five patients), or gram-negative organisms alone (two patients). Debridement and pump implantation were performed in one stage. On an outpatient basis, the pumps were filled with amikacin in a concentration determined by each patient's serum level. Duration of therapy was based upon cessation of drainage and erythrocyte sedimentation rate. During therapy, serum amikacin levels ranged from less than 2.5 micrograms/ml to 8.2 micrograms/ml. The amikacin concentration in the wound drainage was always greater than the upper limits of what could be measured (greater than 55 micrograms/ml to greater than 5,000 micrograms/ml). There were no cases of ototoxicity and one case of minimal renal toxicity (posttreatment creatinine clearance of 66 ml per minute; normal equal to 70 ml per minute). Length of therapy ranged from 32 to 140 days (mean equal to 63 days). Length of hospitalization ranged from five to 52 days (mean equal to 24 days). Drainage in all patients stopped during therapy, but resumed in three patients after pump removal--in two patients, for brief periods of time, and in one patient, it continues. Twelve patients have posttreatment erythrocyte sedimentation rates less than or equal to 20 mm per hour.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Flexible intramedullary nailing of subtrochanteric fractures of the femur. A multicenter analysis.

In a retrospective, multicenter analysis, 79 subtrochanteric fractures of the femur were treated with flexible intramedullary nails. Seventy fractures were traumatic in origin, three were pathologic, and six occurred in spinal cord patients. All of the fractures healed, and there were no fixation failures. Thirteen patients (16%) required adjunctive internal fixation, bone grafts, or postoperative traction. Shortening greater than 1 cm occurred in four patients (5%). Reoperation with one week of surgery was necessary in eight patients (10%). The single greatest complication was knee complaints, which occurred in 17 patients (21.5%). However, only six of these patients required revision prior to fracture union. In one patient a deep wound infection developed, which eventually healed without evidence of osteomyelitis. All patients who were ambulatory before their fracture were able to bear weight.

Adolescent↗

Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets.

The purpose of this study was to investigate the response of human blood platelets to fluoride at different pH. The results were as follows. (1) Fluoride induced secretion faster and at a lower concentration when pH was lowered. (2) Platelets exposed to 2 mM-fluoride at 0 degrees C at pH 5.3 underwent secretion when first pH and then temperature was raised, although no secretion was seen at 2 mM-fluoride concentration in the absence of the preincubation at low pH. (3) The concentration of [14C]ATP in platelets decreased steeply in response to fluoride before induction of secretion. Addition of antimycin blocked or partly inhibited secretion. Fluoride thus exerts an inhibitory effect on platelet glycolysis before induction of secretion. (4) Fluoride accumulated in the platelet pellet by a time course that preceded secretion. The accumulation was faster and greater at pH 6 than at 7.4. These four points are taken as indirect evidence that fluoride has to penetrate to the interior of the platelet to induce secretion. The activation takes place over a wide range of acid pH in contrast with induction of platelet function via the outside of the plasma membrane. In addition evidence is presented that the salvage pathway may under special circumstances play an important role in the re-synthesis of platelet adenine nucleotides.

Adenosine Triphosphate↗

Metabolic aspects of the secretion of stored compounds from blood platelets. V. Effect of ionophore A23187 on washed platelets.

1. The A23187-induced secretion of preabsorbed serotonin from human blood platelets at 37 degrees C is studied. Preincubation at the same temperature before the addition of ionophore is necessary for maximal release induction. When total incubation time is kept constant, longer time with ionophore results in a smaller decrease in the level of metabolic ATP and increase in metabolic ATP and increase in metabolic IMP. This coincides with the reduction in secretion, but statistical treatment of the results suggests that the reduced secretion only partially explains the reduced drop in metabolic ATP, and that therefore a resynthesis of metabolic ATP from IMP may have taken place. 2. In some experiments induction of secretion takes place over a very narrow range of ionophore concentration. 3. When K+ substitutes for Na+ in the extracellular medium, the need for preincubation for maximal secretion becomes less evident, and at times is abolished, while there is still a significant increase in the metabolic ATP level by prolonged incubation with ionophore. 4. A reduction in secretion is observed with metabolic blockers when the ionophore is added after preincubation, but to a much less degree than when secretion is induced by thrombin, in spite of a great reduction in the level of metabolic ATP. This may partly be explained by the increase in secretion induction by A23187 in the presence of inhibitors when the ionophore is added in the cold, suggesting that the inhibitor may cause "weakening" of the platelets' "resistance" to induction of secretion by ionophore. 5. When the effect of Ca2+ and of Mg2+ on the level of intermediates of the TP leads to hypoxanthine conversion is studied, it is evident that the addition of Ca2+ causes enhanced IMP accumulation and a reduction in the level of inosine plus hypoxanthine, while Mg2+ has the opposite effect. This suggests that the two metals affect the enzymes of the IMP leads to hypoxanthine conversion differently. 6. Indomethacin inhibits secretion induced by A23187, suggesting that prostaglandin intermediates may amplify the ionophore-induced release. The adenine nucleotide metabolism is not affected. 7. The results indicate that there is an indirect, rather than direct, link between the major metabolic changes and the secretion induced by A23187, but that the ionophore may cause intracellular changes which are not connected to its effect as release inducer.

Adenine↗

Metabolic aspects of the secretion of stored compounds from blood platelets. IV. Effects of ionophore X537A on washed platelets.

1. X537A at concentrations below 10 muM can liberate platelet serotonin from washed human platelets without inducing the platelet release reaction. Up to 100% of serotonin preabsorbed by the platelets can be liberated before initiation of the release reaction. 2. Concentrations of X537A above 10muM initiate the platelet release reaction, with a maximum release of adenine nucleotides and platelet factor 4 antigen comparable to that obtained with 1.25 units thrombin/ml. 3. The changes in ATP metabolism at the concentration necessary for X537A-induced release are more profound than those in platelets exposed to concentrations of thrombin or A23187 giving the same degree of release, and approach those seen with high concentrations of A23187. At concentrations where serotonin is liberated but no adenine nucleotide or platelet factor 4 antigen is released, short time incubation causes no change in the level of metabolic ATP.

Adenine Nucleotides↗