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Biomedical subjects

E J Baker

Publications and source records attributed to E J Baker.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

Double-outlet right ventricle: morphologic demonstration using nuclear magnetic resonance imaging.

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination. Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were less than 90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact. In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortem findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy. In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management.

Angiography

Transcatheter embolization in the treatment of coronary artery fistulas.

Seven patients with a coronary artery fistula underwent percutaneous transcatheter embolization (five were male and two female; the age range was 2 to 67 years [median 17]). Three patients were symptomatic. The left to right shunt ranged from 1.6 to 2.6:1. In six patients, the fistula was an isolated congenital anomaly; in one, it was acquired. The fistula arose from branches of the left (n = 5) and right (n = 2) coronary arteries and drained to the right ventricle (n = 2), right atrium (n = 2), coronary sinus (n = 1), pulmonary artery (n = 1) and a bronchial artery (n = 1). Different embolization techniques were used to occlude eight feeding arteries. The embolization materials included a detachable balloon (n = 3), coaxial embolization with platinum microcoils (n = 3), a combination of detachable balloon and microcoil (n = 1) and standard steel coils (n = 1). Satisfactory occlusion was achieved in six patients. In one case, the valve of the detachable balloon was damaged, resulting in early balloon deflation and a residual fistula. There were no associated complications in any patient. Follow-up investigation by Doppler ultrasound or coronary angiography 4 months to 4 years later showed that permanent occlusion was achieved in all six patients in whom embolization was initially successful. Transcatheter embolization should be considered the treatment of choice for coronary artery fistulas.

Adolescent

Costal fringe.

Costal fringe consists of a bandlike pattern of venous telangiectases along the anterolateral costal margins. It is a common and easily recognized entity, usually seen in elderly men. Association with underlying disease is not well established. To assess the frequency of costal fringe in a healthy young adult population, we examined 1523 active duty Air Force personnel (1203 men and 320 women) between the ages of 17 and 34 years. All subjects were human immunodeficiency virus seronegative; none had known hyperestrogenic or other disease states. Costal fringe was present in only three individuals, all men, a frequency of 0.2%. Costal fringe is a rare finding in healthy young adults.

Adolescent

Magnetic resonance imaging of the great arteries in infants.

Sixty infants, aged 1-48 (median 8) weeks, with suspected congenital heart disease underwent a morphological evaluation of the great arteries using magnetic resonance imaging at 1.5 Tesla. Cross-sectional echocardiography was performed in all infants, angiography in 33 and surgery in 44. Multiple sections, 5 mm thick and gated to the patients' electrocardiogram were acquired in standard and oblique imaging planes. Ventriculo-arterial connexions were correctly identified in 54 infants (6 did not have intracardiac imaging performed) and an accurate description of the relationships of the great arteries was made in all. Magnetic resonance imaging clearly demonstrated normal and hypoplastic pulmonary arteries to the level of the first hilar branches and was better than echocardiography at confirming the presence or absence of central intrapericardial pulmonary arteries in 4 infants with pulmonary atresia. All parts of the thoracic aorta were accurately demonstrated and, in 23 infants with clinical suspicion of aortic coarctation, magnetic resonance images provided more information than echocardiography. Magnetic resonance imaging accurately demonstrates great arteries non-invasively supplementing echocardiographic and angiographic findings. In many cases, it replaces the need for invasive investigations.

Aorta, Thoracic