Examination of the skin barrier repair/wound healing process using a living skin equivalent model and matrix-assisted laser desorption-ionization-mass spectrometry imaging.

OBJECTIVE: Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids directly involved as potential biomarkers. These biomarkers may be used to determine whether an in vivo wound is going to heal for example if infected. METHODS: An in vitro LSE model was wounded with a scalpel blade and assessed at day 4 post-wounding by histology and MALDI-MSI. Samples were sectioned at wound site and were either formalin-fixed paraffin-embedded (FFPE) for histology or snapped frozen (FF) for MSI analysis. RESULTS: The combination of using an in vitro wounded skin model with MSI allowed the identification of lipids involved in the skin barrier repair/wound healing process. The technique was able to highlight lipids directly in the wound site and distinguish differences in lipid distribution between the epidermis and wound site. CONCLUSION: This novel method of coupling an in vitro LSE with MSI allowed in-depth molecular analysis of the skin barrier repair/wound healing process. The technique allowed the identification of lipids directly involved in the skin barrier repair/wound healing process, indicating these biomarkers may be potentially be used within the clinic. These biomarkers will help to determine, which stage of the skin barrier repair/wound healing process the wound is in to provide the best treatment.

Antibacterial activity and mode of action of tert-butylhydroquinone (TBHQ) and its oxidation product, tert-butylbenzoquinone (TBBQ).

OBJECTIVES: The antioxidant tert-butylhydroquinone (TBHQ) is a food additive reported to have antibacterial activity, and may therefore have application in the healthcare setting. This study sought to characterize the antibacterial activity and mode of action of TBHQ and its oxidation product, tert-butylbenzoquinone (TBBQ). METHODS: The stability of TBHQ/TBBQ was studied in buffer. Susceptibility testing was performed by broth microdilution, and killing and lytic activity were evaluated by viable counting and culture turbidity measurements. Mode of action studies included following the incorporation of radiolabelled precursors into macromolecules. The effect of TBHQ/TBBQ upon bacterial and mammalian membranes was assessed using the BacLight(TM) assay and by monitoring the haemolysis of equine erythrocytes. RESULTS: TBHQ underwent oxidation in solution to form TBBQ. When oxidation was prevented, TBHQ lacked useful antibacterial activity, indicating that TBBQ is responsible for the antibacterial activity attributed to TBHQ. TBBQ demonstrated activity against Staphylococcus aureus SH1000 (MIC 8 mg/L) and against a panel of clinical S. aureus isolates (MIC90 16 mg/L). TBBQ at 4× MIC caused a >4 log10 drop in cell viability within 6 h without lysis, and eradicated staphylococcal biofilms at 8× MIC. TBBQ did not display preferential inhibition of any single macromolecular synthetic pathway, but caused loss of staphylococcal membrane integrity without haemolytic activity. CONCLUSIONS: TBBQ is responsible for the antibacterial activity previously ascribed to TBHQ. TBBQ prompts loss of staphylococcal membrane integrity; it is rapidly and extensively bactericidal, but is non-lytic. In view of the potent and selective bactericidal activity of TBBQ, this compound warrants further investigation as a candidate antistaphylococcal agent.

Assessment of the antimicrobial activity of acellular vascular grafts.

Several studies have reported biological vascular grafts to be more resistant to microbial infection than synthetic counterparts in vivo. Indeed, small intestinal submucosa (SIS) materials have previously been reported to be antimicrobial. The aim of this study was to assess the antimicrobial activity and the ability to resist biofilm formation of a novel acellular vascular graft and compare it to commercially available alternatives using a range of organisms: MRSA, MSSA, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Candida albicans. This was achieved using a modified disk diffusion assay and extraction of the materials into solution followed by minimum inhibitory concentration assays. To assess resistance to biofilm formation a novel biofilm assay was developed which compared the total colony forming units (CFU) recovered from each material and identification of the percentage of CFU which were loosely attached, residing within the biofilm or attached to the biomaterial. The results indicated a lack of antimicrobial activity for all materials tested, including SIS. The biological materials were more resistant to the formation of a biofilm compared to Dacron.

Chloracne in seven organic chemists exposed to novel polycyclic halogenated chemical compounds (triazoloquinoxalines).

Chloracne is an acneiform eruption caused though poisoning by aromatic compounds (usually halogenated) showing a specific molecular configuration. We describe an outbreak of chloracne among seven discovery chemists who synthesized novel polycyclic halogenated chemical compounds which were classified as triazoloquinoxalines, not known to be chloracnegenic. The diagnosis of chloracne, made clinically, elicited a thorough risk assessment and monitoring programme by the occupational health department. The chemists were investigated by serum excretion rates, skin sampling for Propionibacterium acnes, skin biopsy and laboratory blood investigations. Sebum excretion was normal in five cases, raised in one case and severely reduced in another. Skin levels of P. acnes were normal in all patients except for the one subject who had low sebum excretion, in whom they were undetectable. One subject had a slightly raised serum level of alanine aminotransferase. There were no other signs of systemic toxicity. Two subjects were treated with an oral antibiotic, two received topical therapy only and three required no treatment at all. The patients have had thorough health surveillance at 6-monthly and yearly intervals. In each case the chloracne mostly resolved within 18-24 months although on examination about 3 years later, five of the seven still showed minor changes of chloracne. This outbreak emphasizes the need for vigilance in discovery science. The triazoloquinoxalines were not previously recognized as being chloracnegens although their chemical characteristics were subsequently identified as being in keeping with other chemicals that can cause chloracne. Chloracne can be a difficult diagnosis to make when it occurs in a novel setting: occupational physicians and dermatologists need to be vigilant when dealing with unusual eruptions in discovery chemists.

Intravascular ultrasound imaging in acute aortic dissection.

OBJECTIVES: This study was performed to determine the potential of intravascular ultrasound in the detection and delineation of aortic dissection. BACKGROUND: Intravascular ultrasound is a new technique capable of displaying real-time cross-sectional images of arterial vasculature. Its clinical use has been explored mostly in coronary and peripheral arterial circulation. METHODS: Intravascular ultrasound imaging of the aorta was performed using a 20-MHz ultrasound catheter in 28 patients with suspected aortic dissection. All patients underwent contrast angiography; 7 had computed tomography; and 22 had transesophageal echocardiography. RESULTS: Imaging of the aorta from the root level to its bifurcation was performed in all patients in an average of 10 min. No complications occurred. Dissection was present in 23 patients and absent in 5. In the patients without dissection, intravascular ultrasound revealed normal aortic anatomy. In all 23 patients with dissection, intravascular ultrasound demonstrated the intimal flap and true and false lumena. The longitudinal and circumferential extent of aortic dissection, contents of the false lumen, involvement of branch vessels and the presence of intramural hematoma in the aortic wall could also be identified. In cases where aortography could not define the distal extent of the dissection, intravascular ultrasound did. CONCLUSIONS: Our experience in this series of patients with aortic dissection indicates that intravascular ultrasound could be valuable in the identification and categorization of aortic dissection and in the description of associated pathologic changes that may be clinically important. It can be performed rapidly and safely and could serve as an alternative or adjunct diagnostic procedure in patients with aortic dissection.

An observer-blind parallel-group, randomized, multicentre clinical and microbiological study of a topical clindamycin/zinc gel and a topical clindamycin lotion in patients with mild/moderate acne.

INTRODUCTION: A topical acne treatment in which clindamycin phosphate equivalent to 1% clindamycin is presented in a gel formulation has received marketing authorizations in a number of EU and non-EU countries. Clindamycin/zinc gel contains zinc acetate in a formulation that reduces systemic absorption of clindamycin through the skin. OBJECTIVES: To compare the efficacy and safety of a 1% clindamycin/zinc gel when applied to the face once daily or twice daily with a 1% clindamycin lotion applied twice daily for 16 weeks in patients with mild to moderate acne vulgaris. METHODS: This was a randomized, comparative, observer-blind, parallel-group, multicentre study involving 246 acne patients. RESULTS: The study demonstrated therapeutic similarity between clindamycin/zinc gel applied once and twice daily with clindamycin lotion applied twice daily. All three regimens produced a gradual and time-dependent reduction in inflamed lesions, non-inflamed lesions and overall grade. Side effects were similar and minimal, consisting predominantly of mild irritant dermatitis. All regimes produced a time-related significant reduction in skin surface and follicular Propionibacterium spp. and Micrococcaceae. The emergence of resistant strains was less than 5% and was similar with all three regimes. CONCLUSION: The equivalent efficacy and safety of clindamycin/zinc gel either once or twice daily to clindamycin lotion twice daily has been demonstrated. It is suggested that a treatment regime of one application per day may significantly enhance compliance and thus treatment success in acne patients.

Treatment of multiple cerebral emboli from an ulcerated, thrombogenic ascending aorta with aortectomy and graft replacement.

Multiple studies link aortic arch atheroma as a donor site for cerebral emboli. However, treatment of this condition remains controversial. We report a patient with recurrent brain emboli from an ulcerated, thrombogenic aorta treated with aortectomy and graft replacement.

Homograft repair of a tuberculous pseudoaneurysm of the ascending aorta.

A 34-year-old HIV-positive black man with pulmonary tuberculosis developed progressive widening of the mediastinum. Evaluation by CT and two-dimensional echocardiography demonstrated a large saccular aneurysm of the ascending aorta. This was repaired with a 26-mm aortic homograft using deep hypothermic circulatory arrest. The microbiology of the aneurysm contents showed this to be a tuberculous pseudoaneurysm.

Clinical benefits of endoscopic vein harvesting in patients with risk factors for saphenectomy wound infections undergoing coronary artery bypass grafting.

OBJECTIVE: The influence of endoscopic harvesting techniques on the prevalence of leg-wound complications after coronary artery bypass grafting remains to be defined for patients at high risk for the development of wound infections. METHODS: Among 1473 patients undergoing coronary artery bypass grafting who had the saphenous vein harvested by either a continuous incision or skip incisions leaving intact skin bridges, we determined the prevalence of wound infections to be 9.6%. The following variables were entered into logistic regression analysis to identify significant risk factors that might be predictive of wound infection: diabetes, peripheral vascular disease, obesity, renal failure, steroid use, age, sex, and type of closure. We then prospectively randomized 132 patients found to be at high risk of wound infection to either endoscopic vein harvesting or a continuous open incision. RESULTS: Univariate analysis showed female sex (P =.04), diabetes (P <.001), and obesity (P <.001) to be predictors of wound infection. In a multivariate model diabetes (P =.02) and obesity (P =.001) were independent predictors. In patients at high risk, the prevalence of wound infection was 4.5% for the endoscopic group versus 20% for the open group (P =.01). Vein procurement time was greater in the endoscopic group (65 minutes vs 32 minutes, P <.001), as was the number of vein repairs required (2.5 vs 0.6, P <.001). CONCLUSION: The use of endoscopic vein harvesting decreases the prevalence of postoperative leg-wound infections in high-risk patients with diabetes and obesity. Whether this translates into an economic benefit that justifies the additional cost of that technology requires further analysis.

Clinical and hemodynamic performance of the Ionescu-Shiley valve in the small aortic root. Results in 117 patients with 17 and 19 mm valves.

The Ionescu-Shiley pericardial valve was our bioprosthetic valve of choice between 1981 and 1985 for patients in whom the aortic anulus could not accept a valve larger than 19 mm in outer diameter or in whom the avoidance of warfarin sodium (Coumadin) was important. A series of 117 consecutive patients who received 17 or 19 mm valves for isolated aortic valve replacement or aortic valve replacement combined with coronary artery bypass grafting or other valvular procedures was analyzed. Overall, 74% of the patients were female, with a mean age of 70.9 years and a body surface area of 1.67 +/- 0.19 m2; 92.3% were in New York Heart Association class III-IV, and the operation was urgent or emergent in 46%. The operative mortality rate was 7.7%, with no deaths in patients undergoing isolated elective first-time aortic valve replacement. Mean follow-up for survivors was 2.5 years (10 to 62 months). There were 20 late deaths, of which three were valve related, three were due to sudden death or arrhythmias, and two were due to persistent heart failure. The actuarial survival rate at 5 years was 68%. Clinical follow-up revealed a low incidence of valve-related complications, and 96.4% of survivors were in class I-II. Postoperative echocardiography before hospital discharge revealed a maximum instantaneous gradient of 18.4 +/- 3.0 mm Hg in five patients having a 17 mm valve and 31.3 +/- 12.7 mm Hg in 20 patients having a 19 mm valve. Doppler echocardiography was performed in 22 patients at a mean follow-up of 39.3 +/- 11.7 months. The maximum instantaneous gradient was 25 +/- 17.2 mm Hg for 17 mm and 17.41 +/- 5.4 mm Hg for 19 mm valves at late follow-up. The effective orifice area was 0.85 +/- 0.1 cm2 for 17 mm and 1.21 +/- 0.21 cm2 for 19 mm valves. This study defines the normal range of Doppler echocardiographic transprosthetic gradients for the Ionescu-Shiley valve and confirms that low operative mortality and excellent clinical improvement can result from the use of small Ionescu-Shiley valves in elderly patients despite moderate postoperative transvalvular gradients.

Successful management of left ventricular rupture following myocardial revascularization.

Left ventricular (LV) rupture is a common cause of death following myocardial infarction, but it is rarely noted following coronary bypass surgery. This is true despite the increasing number of coronary bypass operations performed for postinfarction angina, often following transmural infarction. A 59-year-old woman underwent successful repair of left ventricular free-wall rupture that occurred after coronary surgery performed for postinfarction angina. To our knowledge, this is the first report to establish the feasibility of successful surgical repair of left ventricular free-wall rupture in the postoperative patient with tamponade or intrathoracic bleeding.

Clinical and hemodynamic performance of the 19-mm Carpentier-Edwards porcine bioprosthesis.

Because of concerns about the hemodynamic performance of 19-mm porcine valves, we retrospectively reviewed the clinical results and echocardiographic studies of 52 consecutive patients who received a 19-mm Carpentier-Edwards porcine bioprosthesis (model 2625) for aortic valve replacement from 1986 through 1991. Nearly 87% of the patients were women, the mean age was 69 years, and the mean body surface area was 1.63 +/- 0.27 m2. Seventy-three percent of the patients had pure aortic stenosis, 96% were in New York Heart Association classes III and IV, and 56% underwent urgent or emergent operation. Overall hospital mortality was 7.7% with a late mortality of 8.3% at a mean follow-up of 25 +/- 18 months. No patient experienced a valve-related complication, and 95% of surviving patients were in New York Heart Association classes I and II. Two-dimensional and Doppler echocardiography performed during the first postoperative week revealed a maximal instantaneous gradient of 44.7 +/- 13.0 mm Hg. In 43 patients for whom additional data were available, the mean gradient was 26.4 +/- 8.2 mm Hg with an effective orifice area of 0.85 +/- 0.18 cm2. This study defines the normal range of postoperative gradients across the 19-mm Carpentier-Edwards porcine valve and demonstrates that patients receiving this valve can achieve significant clinical improvement despite the presence of high transvalvular gradients measured by echocardiography.

Use of self-adhesive external defibrillator pads for complex cardiac surgical procedures.

We describe a useful technique for the management of life-threatening arrhythmias that occur during complex or reoperative cardiac surgical procedures when internal defibrillation cannot be achieved. Two self-adhesive external pads are attached to the patient before draping to enable the delivery of current for defibrillation or cardioversion without the need for removal of adhesive surgical drapes and the cumbersome use of external defibrillator paddles.

Pericardiocentesis under two-dimensional echocardiographic guidance in loculated pericardial effusion.

Pericardiocentesis to relieve tamponade from a loculated pericardial effusion in patients following cardiac surgery is greatly aided by two-dimensional echocardiographic imaging guidance. This technique delineates the fluid distribution and the site of adhesions, defines the path for introduction of an aspiration needle, alerts to the possibility of myocardial contact, and helps in positioning the drainage catheter. Two-dimensional echocardiographic imaging can be performed at the patient's bedside, and the images are easy to interpret. This technique simplifies pericardiocentesis and helps to avoid complications.

Neurological complications of coronary revascularization.

In a series of 3,206 consecutive coronary artery bypass procedures performed between 1976 and 1981, 89 patients died (2.8% mortality) and 32 patients (1%) suffered major neurological syndromes. Among the latter patients, four distinct groups were identified. Group 1 consisted of 10 patients who remained unresponsive after operation. In Group 2 were 10 patients who awakened after operation but had clinical evidence of focal cerebral infarction. Group 3 included 6 patients who were initially intact neurologically but in whom neurological deficits later developed. In Group 4 were 6 patients who had severe mental aberration but no focal neurological deficits. The incidence of coma or focal deficit occurring without a lucid interval (Groups 1 and 2) was 0.62%, and these patients had a 30% mortality. Causative factors were suspected in 70% of the patients in Groups 1 and 2, and included atheromatous embolism, perioperative hypotension, carotid artery occlusive disease and air embolism. The outcome was poor for unresponsive patients, with 70% dying or remaining comatose, but nearly all of the patients with focal deficits or severe mental aberration demonstrated notable improvement.

Methemoglobinemia from intravenous nitroglycerin: a word of caution.

The dose of intravenously administered nitroglycerin (IV NTG) used to control ischemic chest pain usually is limited by hypotension from decreased preload. Herein we describe 2 patients who tolerated IV NTG without hemodynamic compromise but in whom severe impairment of blood oxygen content developed from methemoglobinemia noted during coronary bypass surgery. Methemoglobinemia must be suspected if chocolate-brown blood is encountered despite a normal arterial oxygen tension and calculated oxygen saturation. Before a methemoglobin level is available, the extent of hypoxemia can be determined by an oximetric oxygen saturation and therapy begun with intravenous administration of methylene blue. These case reports focus attention on the potential deleterious effects of undetected hypoxemia from methemoglobinemia in patients being stabilized with high-dose IV NTG for urgent cardiac surgery.

Surgical treatment of systemic atheroembolism from the thoracic aorta.

BACKGROUND: Surgical procedures performed exclusively for atheroembolic events arising from the thoracic aorta rarely have been reported. Presented here are 2 patients who underwent successful operation for these problems. METHODS: The clinical presentation, diagnostic evaluation and surgical approach to 2 patients with different embolic sources in the thoracic aorta are presented. One patient had experienced three strokes and was noted by multiplane transesophageal echocardiography to have protruding atheromas with ulcerations in the transverse arch and origin of the brachiocephalic vessels. The transverse arch was replaced using hypothermic circulatory arrest with individual reimplantation of the brachiocephalic vessels. The second patient presented with "blue toe" syndrome from mobile atheromas in the mid-descending thoracic aorta defined by transesophageal echocardiography. A localized debridement was performed using simple aortic cross-clamping. RESULTS: Both patients had uneventful postoperative courses and had no further atheroembolic events. CONCLUSIONS: When standard diagnostic modalities do not delineate an embolic source for either stroke or peripheral embolization, transesophageal echocardiography is recommended as an excellent means of identifying atheromas in the thoracic aorta that could be the source for emboli. Once these lesions are identified, a surgical procedure should be performed to prevent further embolization.

Successful repair of postoperative ascending aortic mycotic false aneurysms using circulatory arrest.

Mediastinal wound infections following open-heart operations are successfully managed in most patients by aggressive debridement and placement of substernal drainage catheters or application of omental or muscle flaps. Nonetheless, the involvement of foreign bodies, such as felt pledgets adjacent to cardiac structures, can result in infections that persist despite flap coverage and can present as mycotic false aneurysms of the ascending aorta. We present the cases of 3 patients who underwent successful repair of such aneurysms late after surgical treatment of mediastinal wound infections. We describe our technique of repair using groin cannulation for bypass, moderate hypothermia, and circulatory arrest to improve exposure and minimize bleeding.

Efficacy of retrograde coronary sinus cardioplegia in patients undergoing myocardial revascularization: a prospective randomized trial.

The efficacy of retrograde coronary sinus cardioplegia (RCSC) administered through the right atrium compared with aortic root cardioplegia (ARC) has not been examined critically in patients undergoing coronary artery bypass grafting (CABG). Twenty patients having elective CABG were randomized prospectively to receive cold blood ARC (Group I, 10 patients) or cold blood RCSC (Group II, 10 patients). Patient demographics were similar in both groups. Ventricular function was assessed preoperatively by radionuclide ventriculography and postoperatively by simultaneous hemodynamic and radionuclide ventriculographic studies with volume loading. There was no change in ejection fraction (EF) (preoperative versus postoperative value) in Group I (50 +/- 6% versus 53 +/- 6%) but in group II, at similar peak systolic pressure and similar left ventricular end-diastolic volume index (LVEDVI), LVEF improved significantly (49 +/- 6% versus 60 +/- 12%, p less than 0.05). Postoperative ventricular function (stroke work index versus EDVI) for the left ventricle and right ventricle were similar in both groups. Evaluation of postoperative LV systolic function (end-systolic blood pressure versus end-systolic volume index) and diastolic function (pulmonary capillary wedge pressure versus EDVI) were also similar in both groups. Retrograde coronary sinus cardioplegia is as effective as ARC for intraoperative myocardial protection, and provides excellent postoperative function in patients undergoing elective CABG.

Ruptured sinus of Valsalva aneurysm simulating endocarditis.

A previously healthy, 31-year-old man was evaluated in the emergency department after being violently assaulted. A harsh, continuous murmur was noted on physical examination. Transthoracic and transesophageal echocardiograms were interpreted as showing a ruptured sinus of Valsalva aneurysm with a shunt into the right atrium and a tricuspid valve vegetation. The patient was treated with antibiotics for presumed endocarditis. Subsequent echocardiographic and surgical evaluation showed no evidence of past or present endocarditis. Rather, the sinus of Valsalva aneurysm and rupture gave the appearance of a valvular mass. This report shows some of the potential pitfalls in the delineation of abnormalities related to sinus of Valsalva aneurysms and rupture.