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Biomedical subjects

E J Baker

Publications and source records attributed to E J Baker.

At least 37 records · Page 2Linked to original sources
PubMed1995

In vitro percutaneous absorption of arildone, a highly lipophilic drug, and the apparent no-effect of the penetration enhancer Azone in excised human skin.

PURPOSE: Arildone, a novel lipophilic antiviral drug when evaluated in Clinical Trials showed limited skin absorption and antiviral efficacy. These studies were conducted to explain the apparent poor absorption characteristics and attempt to promote skin absorption by using Azone, a penetration enhancer. METHODS: Standard in vitro skin permeation methods using excised human skin were employed to characterise the absorption of Arildone. 14C-Arildone was used to estimate the distribution in skin layers by scintigraphic and autoradiographic procedures. RESULTS: The aqueous solubility and distribution constant values for Arildone were 2 micrograms ml-1 and 5 x 10(5) (isopropyl myristate/water), respectively. Absorption through full thickness skin or stratum corneum-viable epidermal membranes (diffusional resistant dermis removed), from a propylene glycol vehicle, was slow and the addition of Azone had no effect on the permeation rate. Distribution studies showed accumulation of Arildone in the stratum corneum. The concentration of Arildone in the viable epidermis was estimated from sectioning the skin and was found to be in sufficient amounts (400 micrograms cm-3) to have potential antiviral activity. CONCLUSIONS: The apparent accumulation of Arildone in the stratum corneum suggested that the hydrophilic skin region presented the main barrier to permeation. Azone which affected the permeability of the stratum corneum was therefore not effective at enhancing Arildone absorption. Vehicles which readily permeate and enhance the transfer of lipophilic drugs from the stratum corneum into the viable epidermis were recommended.

Aged↗
PubMed1995

Tolerance of the developing heart to ischemia: impact of hypoxemia from birth.

Many infants who require cardiac surgery have cyanotic heart disease. We assessed the relative tolerances to ischemia of hearts from immature normoxemic rabbits versus hearts from immature rabbits subjected to hypoxemia since birth. Normoxemic animals were raised from birth in an environment where the inspired fractional concentration of oxygen (FIO2) was 0.21; for the hypoxemic studies FIO2 was reduced to 0.09. Hearts (n = 6/group) from normoxemic and chronically hypoxemic rabbits at 7-12, 21-28, 35-44, and 51-56 days of age underwent aerobic "working" perfusion with Krebs bicarbonate buffer, and cardiac function was measured. Hearts were then arrested by a 3-min infusion with either cold (14 degrees C) Krebs buffer (hypothermia alone group) or St. Thomas' Hospital II solution (hypothermia plus cardioplegia group) before 6 h of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic creatine kinase leakage and recovery of function were measured. For hearts protected with hypothermia alone, recovery of aortic flow was better in hearts hypoxemic from birth compared with normoxemic controls at 7-12 days (78 +/- 7 vs. 60 +/- 6%, P < 0.05) and 21-28 days old (81 +/- 12 vs. 26 +/- 28%, P < 0.05). Protection with hypothermia plus cardioplegia was also better in hearts hypoxemic from birth compared with normoxemic controls at 7-12 days (74 +/- 8 vs. 63 +/- 10%, P < 0.05) and 21-28 days old (84 +/- 3 vs. 71 +/- 5%, P < 0.05). Protection with hypothermia alone and hypothermia plus cardioplegia was no different within chronically hypoxemic age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Soft tissue abscesses associated with parenteral drug abuse: presentation, microbiology, and treatment.

Abscess formation at the site of drug injection is the commonest infectious complication in drug addicts. This study characterizes the clinical presentation of the condition, its current microbiology, and treatment outcome. All patients presenting for treatment of soft tissue abscesses associated with parenteral drug abuse over a 21-month period were studied. Sixty-six patients with 70 subcutaneous abscesses after injection of cocaine (85%), heroin (5%), or unreported drugs (10%) were identified. Only 42% were febrile (T > 37.5 degrees C), 54 percent had leukocytosis, and 47 percent had wound fluctuance. Wound cultures (243 isolates in 57 patients) grew predominately anaerobes (143 isolates) and facultative gram-positive cocci (88 isolates). Twenty-six blood cultures were obtained, and five (19%) were positive, two with the same bacteria isolated from the wound. Of the patients tested, 29 percent were positive for hepatitis B surface antigen and 9 percent for HIV. Simple incision and drainage was effective in all cases. Classical signs and symptoms of infection and abscess formation may be absent in this patient population. Many of these patients carry other blood-borne infections which the health professional must guard against. Cocaine injection, and "mixed" aerobic-anaerobic infections predominated, in contrast to earlier reports, when narcotics and aerobes predominated. Simple incision and drainage is adequate treatment; antibiotics, when given, should cover gram-positive and anaerobic bacteria; gram-negative coverage is unnecessary.

Abscess↗
PubMed1994

Effect of introducing balloon dilation of native aortic coarctation on overall outcome in infants and children.

The outcome of 40 consecutive newborns and children with normal cardiac connections presenting with unoperated (i.e., no previous surgical or balloon dilation treatment) aortic coarctation since the introduction of balloon dilation as a treatment option (group A) was compared retrospectively with that of a similar cohort of 38 patients (group B) presenting in the period immediately before the introduction of balloon dilation. Group A consisted of 18 newborns (< 30 days) and 22 children and Group B consisted of 20 newborns and 18 children. In group A, 30 patients had balloon dilation but 10 underwent surgery because of parental preference, unfavorable anatomy or for logistic reasons. Group B had conventional surgical repair by various methods. All patients were followed up clinically by Doppler echocardiography and, when possible, by magnetic resonance imaging. Repeat cardiac catheterization was only performed in those with suspected recoarctation. Survival and freedom from reintervention were investigated using Kaplan-Meier analysis. Patients of all ages in group A and those who had balloon dilation were at higher risk for reintervention (25 and 30%, respectively, at 1 year) than those in group B or those who had surgery (20 and 18%, respectively, at 1 year). Mortality was not significantly different between groups A and B, but there were 2 neonatal deaths directly attributable to the dilation procedure. Two patients developed aneurysms after dilation. Balloon dilation is an effective treatment for unoperated coarctation, but the recoarctation rate appears to be higher than for surgery.

Adolescent↗
PubMed1994

Calcium and cardioplegic protection of the ischemic immature heart: impact of hypoxemia from birth.

Because many infants who require cardiac operation have cyanotic heart disease, we determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is optimal to protect the immature rabbit heart hypoxemic from birth during subsequent ischemia. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting chronically hypoxemic (PaO2 = 34 +/- 11 mmHg, SaO2 = 63% +/- 3%) versus normoxemic (PaO2 = 76 +/- 11 mmHg, SaO2 = 92% +/- 3%) immature hearts (7 to 12 days old) during ischemia. Hearts (n = 6 per group) underwent aerobic 'working' perfusion with Krebs bicarbonate buffer and cardiac function was measured. The hearts were then arrested with a 3 minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or modified St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile was observed for recovery of postischemic aortic flow but not for postischemic creatine kinase leakage, with improved protection occurring at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.4 mmol/L, which was significantly better than with hypothermia alone or standard St. Thomas' II solution. We conclude that the existing calcium concentration of St. Thomas' II solution is responsible, in part, for its inadequate protection of immature myocardium hypoxemic from birth during ischemia.

Animals↗
PubMed1994

Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: radionuclide imaging with technetium-99m 2-methoxy isobutyl isonitrile.

OBJECTIVES: We sought to determine the incidence of late perfusion defects attributable to coronary artery mobilization in patients undergoing anatomic correction for complete transposition of the great arteries. BACKGROUND: Anatomic correction (arterial switch procedure) is currently the surgical treatment of choice for complete transposition. From its conception, there has been concern about the impact on myocardial perfusion of the coronary artery mobilization and reimplantation involved in the correction. Previous studies have demonstrated myocardial perfusion defects in patients after correction, although a causal relation between coronary mobilization, and perfusion abnormality has not been established. METHODS: In a case-comparison study designed to test this hypothesis, 29 children underwent imaging with technetium-99m 2-methoxy isobutyl isonitrile (technetium-99m mibi). Ten had undergone anatomic correction (arterial switch group; interval from operation 6.9 +/- 1.42 years [range 4.9 to 9.1]); 9 had required noncoronary open heart surgery for other cardiac lesions (post-bypass group; interval from operation 5.6 +/- 3.6 years [range 1.0 to 13.25]); and 10 had had no surgical procedure (control group). The latter group comprised children with atrial or ventricular septal defects who required a radionuclide study for shunt calculation. Planar studies were performed in all 29 children, and additional tomographic acquisition was achieved in 25. To assess reversibility of perfusion defects both an exercise and a rest planar study were performed in the arterial switch group. RESULTS: Perfusion abnormalities were observed in seven of the nine children in the postbypass group and in all 10 children in the arterial switch group. The frequency of perfusion defects in these two groups was similar, with at least 25% of the tomographic segments reported being abnormal. The control group had significantly fewer defects than the other two groups (p = 0.02), with only 8% of the tomographic segments judged to be abnormal. In all except one patient in the arterial switch group, the segments reported as abnormal on the planar exercise study were either abnormal or equivocal on the rest study, indicating a fixed abnormality. CONCLUSIONS: Although the precise etiology of these perfusion abnormalities cannot be defined from this study, these data suggest that their origin is related more to the insult of open heart surgery itself than to the coronary manipulation involved in the arterial switch procedure. The functional importance requires further study.

Cardiac Surgical Procedures↗
PubMed1994

Percutaneous transcatheter retrieval of misplaced therapeutic embolisation devices.

OBJECTIVE: To assess the incidence and subsequent management of misplaced devices as a complication of therapeutic embolisation procedures. DESIGN: Retrospective review of case notes, cardiac catheterisation reports, and angiograms. SETTING: Tertiary referral centre for congenital heart disease. PATIENTS: 205 consecutive children and adults undergoing therapeutic embolisation for congenital heart disease in the 10 years up to 1 April 1993. This group had 231 therapeutic embolisation procedures at 241 sites using coils, umbrella devices, or detachable balloons. MAIN OUTCOME MEASURES: Incidences of misplacement and retrieval of the device; morbidity and mortality. RESULTS: The incidence of misplacement was 3% (10/332) of devices deployed and 4.3% (10/231) of procedures performed. Retrieval from distal pulmonary arteries was not attempted in two patients, but transcatheter retrieval of coils and umbrellas from systemic and pulmonary vessels, using snares or retrieval baskets, was successful in the remaining eight. There were no deaths or serious sequelae related to the procedure, but one patient required femoral arteriotomy for removal of an umbrella device retrieved only as far as the groin. In four of the five most recent cases, the misplaced device was retrieved and the therapeutic embolisation was completed at the same procedure. CONCLUSIONS: Misplacement of a device during therapeutic embolisation is a recognised complication that can be satisfactorily dealt with by transcatheter retrieval without recourse to surgery. For retrieval to be successful it is important to have a wide selection of retrieval equipment available and to be conversant with its use.

Adolescent↗
PubMed1993

Accelerated poly(A) loss and mRNA stabilization are independent effects of protein synthesis inhibition on alpha-tubulin mRNA in Chlamydomonas.

In Chlamydomonas, the usual rapid degradation of tubulin mRNAs induced by flagellar amputation is prevented by inhibition of protein synthesis with cycloheximide. Evidence is presented that the ability of cycloheximide to stabilize alpha-tubulin mRNA depends on the time of addition. Addition of cycloheximide to cells before induction strongly stabilizes the induced mRNAs, while addition after their synthesis stabilizes them only transiently. Moreover, cycloheximide inhibition does not stabilize the same alpha-tubulin mRNA species in uninduced cells. These results suggest that cycloheximide is not acting to stabilize the induced alpha-tubulin mRNAs simply by preventing ribosome translocation. The stabilized state of tubulin mRNA was found to correlate with its occurrence on smaller polysomes but larger EDTA-released mRNP particles than the unstable state. A second effect of cycloheximide on the metabolism of induced tubulin mRNAs is to accelerate complete poly(A) removal. This effect of cycloheximide inhibition, unlike stabilization, occurs whenever cycloheximide is added to cells, and appears unrelated to stabilization. The effect is shown to be mRNA-specific; poly(A)-shortening on the rbcS2 mRNA is not altered in the presence of cycloheximide, nor do completely deadenylated molecules accumulate. Experiments in which cells were released from cycloheximide inhibition suggest that deadenylated alpha-tubulin mRNAs may be less stable than their polyadenylated counterparts during active translation.

Animals↗
PubMed1993

Tubulin mRNA instability and stabilization by protein synthesis inhibitors are reproducible in nontranslating extracts from Chlamydomonas.

In Chlamydomonas reinhardtii, flagellar amputation stimulates an induction in the synthesis of flagellar proteins which allows the cells to rapidly regenerate their flagella. The induction involves the coordinate accumulation and rapid degradation of a large number mRNAs, including those encoding the tubulins. The post-induction degradation of induced tubulin mRNAs has been shown to differ from the constitutive turnover pathway in two ways: (1) the rate of degradation is accelerated, and (2) degradation is prevented by inhibition of protein synthesis. In this report, it is shown that the post-induction degradation of all deflagellation-induced mRNAs examined is prevented by cycloheximide (CX), suggesting they all may be degraded via the same pathway. A cell-free decay system has been developed to investigate the degradation pathway. At least two characteristics of tubulin mRNA degradation are reproducible in these extracts: (1) endogenous alpha-tubulin mRNA is less stable than constitutive mRNAs in the same extract and (2) alpha-tubulin mRNA in extracts prepared from CX-treated cells (CX extracts) is significantly more stable than it is in extracts from untreated cells (control extracts). This indicates that the mechanism by which CX blocks rapid degradation of tubulin mRNA in vivo is not simply by preventing its translation and suggests the involvement of an altered trans-factor. The difference in tubulin mRNA stability in the two extracts is maintained when the extracts are prepared under conditions that dissociate ribosomes from mRNPs, indicating intact polysome structure is not necessary. Tubulin mRNA-containing polysomes isolated from control and CX extracts are equally stable when assayed alone. However, the polysomes from control extracts are more sensitive to exogenous RNAse treatment than are those from CX extracts, indicating a structural difference. There are no detectable differences in soluble factors that influence tubulin mRNA degradation rate between control and CX extracts; addition of excess soluble factors to either control or CX extracts does not alter the tubulin mRNA degradation in the extract, nor does a simple one-to-one combination of the two extracts result in stabilization or destabilization of the whole population of tubulin mRNAs in the mixture. The deflagellation-induced mRNAs, as a group, are shown to be particularly susceptible to a nuclease activity in extracts, inhibitable by vanadyl ribonucleoside complexes, which does not appear to attack constitutive mRNAs. It is proposed that a structural difference in the tubulin mRNPs produced in the presence and absence of CX underlies their differences in stabilities, and that a common nuclease targets the induced flagellar protein mRNAs.

Animals↗
PubMed1993

Use of a second transcatheter Rashkind arterial duct occluder for persistent flow after implantation of the first device: indications and results.

OBJECTIVE: To assess the efficacy, feasibility, and most appropriate timing of the implantation of a second Rashkind arterial duct occluder because of persistent flow after the first device. DESIGN: A prospective serial Doppler study of patients after the insertion of a Rashkind arterial duct occluder including a subgroup in whom a second device was implanted. SETTING: A tertiary referral centre for congenital heart disease. PATIENTS: 144 patients aged 7 months to 67 years (median 3.38 years) who underwent transcatheter occlusion of patent arterial duct, 20 of whom had attempted implantation of a second device. INTERVENTIONS: Implantation of a second device alongside the first was attempted in 20 of the patients with persistent residual flow. MAIN OUTCOME MEASURES: Successful implantation of a second device, the incidence of complications, and the achievement of complete occlusion on follow up Doppler echocardiography. The time to complete occlusion in the whole group and factors predictive of persistent leak were also analysed. RESULTS: Second devices were successfully implanted in 19 of 20 first attempts and in the remaining patient at the second attempt. Complete occlusion was found in 19 patients at a mean follow up of eight months. The complications included fracture of a guidewire requiring femoral arteriotomy for its removal in one patient and embolisation of a device in another. With a single device, persistence of residual flow six months after implantation and malposition of the device on the aortogram after implantation were predictive of continuing residual patency. CONCLUSIONS: Implantation of a second device is safe, feasible, and effective and should be considered when residual flow persists beyond six months, or if malposition of the first device causes complications such as haemolysis.

Adolescent↗
PubMed1993

Technique of percutaneous laser-assisted valve dilatation for valvar atresia in congenital heart disease.

OBJECTIVE: To investigate the efficacy and safety of transcatheter laser-assisted valve dilatation for atretic valves in children with congenital heart disease. DESIGN: Prospective clinical study. SETTING: Supraregional paediatric cardiology centre. SUBJECTS: Eleven children (aged 1 day-11 years; weight 2.1-35.7 kg) with atresia of pulmonary (10) or tricuspid (one) valve underwent attempted laser-assisted valve dilatation as part of the staged treatment of their cyanotic heart disease. INTERVENTION: After delineating the atretic valve by angiography and/or echocardiography a 0.018 inch "hot tip" laser wire was used to perforate the atretic valve. Subsequently the valve was dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS: Laser-assisted valve dilatation was successfully accomplished in nine children. In two neonates with pulmonary valve atresia, intact ventricular septum, and coexistent infundibular atresia the procedure resulted in cardiac tamponade: one died immediately and one later at surgery. During a follow up of 1-17 months (mean 11) two infants with pulmonary valve atresia and intact ventricular septum died (one with congestive cardiac failure). The remainder are either well palliated and do not require further procedures (three), or are awaiting further transcatheter or surgical procedures because of associated defects (four). CONCLUSIONS: Laser-assisted valve dilatation is a promising adjunct to surgery in this high risk group of patients. It may avoid surgery in some patients, and may reduce the number of surgical procedures in those requiring staged operations.

Balloon Occlusion↗
PubMed1992

Determinants of hemodynamic results of balloon dilation of aortic recoarctation.

Between October 1982 and May 1990, balloon dilation of aortic recoarctation was attempted in 27 patients. In 1 case dilation was not performed owing to suspected aortic perforation. The remaining 26 patients had 30 procedures. The age at the first dilation ranged between 2.6 months and 18.3 years. After dilation, systolic gradient decreased from 49 +/- 17 mm Hg to 20 +/- 17 mm Hg (p less than 0.001). A reduction of gradient to less than or equal to 20 mm Hg occurred after the first dilation in 17 of 26 (65%) patients. Residual gradients between 25 and 80 mm Hg were present in the remaining 9 patients. During follow-up of 2 months to 6.7 years, 5 of 17 patients with a good initial result developed further recoarctation (2 had successful redilation, 2 had reoperation, and 1 is awaiting repeat dilation). Of 9 patients with gradients greater than 20 mm Hg after the first dilation, 1 had successful redilation and 3 had reoperation. The remaining 5 patients are being managed conservatively. 2 patients developed aneurysms after dilation (1 immediately and the other at 2 months). In all, 15 patients (58%) had a good, and 11 (42%) a poor late hemodynamic result. Aortic diameters at different levels of the aortic arch and at the reconstructed isthmus (normalized to the aorta at the level of the diaphragm) were significantly higher in the group with a good late result than in that with a poor one. Balloon/aortic diameter ratio at diaphragm level also had a significant influence on the late results.

Adolescent↗
PubMed1992

Magnetic resonance imaging of hearts with atrioventricular valve atresia or double inlet ventricle.

OBJECTIVE: To investigate the effectiveness and limitations of magnetic resonance imaging in defining cardiac anatomy in patients with double inlet ventricle or atrioventricular valve atresia. DESIGN: Magnetic resonance images were reviewed retrospectively without reference to other morphological data. SETTING: A tertiary referral centre for paediatric cardiology. PATIENTS: 18 patients (aged 8 days to 27 years) with a suspected univentricular atrioventricular connection. METHODS: Imaging by a 1.5 T whole body magnetic resonance system with imaging planes adjusted to individual patient anatomy to best define the cardiac morphology. A complete sequential diagnosis obtained from an independent interpretation of the images was compared with the diagnosis obtained from cross sectional echocardiography and angiocardiography. RESULTS: There was substantial accord between the diagnosis from magnetic resonance alone and that from other methods. In the six instances where there was not accord the magnetic resonance diagnosis was considered to be correct in two cases and incorrect in three cases. In the remaining case no consensus could be reached. In eight patients magnetic resonance imaging provided anatomical information additional to that from other methods. The strengths of magnetic resonance were in imaging the pulmonary arteries and their abnormalities and identifying juxtaposed atrial appendanges but there were some deficiencies in identifying Blalock-Taussig shunts. CONCLUSION: Magnetic resonance imaging provided detailed information about all aspects of cardiac morphology in patients with a suspected diagnosis of univentricular atrioventricular connection. Often it provided additional information to echocardiography. Its use in selected patients should give valuable complementary information.

Adolescent↗
PubMed1992

Mobile encapsulated lipomas.

Mobile encapsulated lipomas are a benign neoplastic process with pronounced mobility in the subcutaneous plane. Characteristic clinical and histologic features differentiate this distinctive entity from similar reactive adipose processes.

Aged↗
PubMed1991

Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium.

Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart.

Age Factors↗