UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to.

Non-occupational post-exposure prophylaxis in Victoria, Australia: responding to high rates of re-presentation and low rates of follow-up.

In Australia, the non-occupational post-exposure prophylaxis service in Victoria (VNPEPS) maintains a database of non-occupational post-exposure prophylaxis (NPEP) use throughout the state. Through the database the service can monitor and respond to patterns of NPEP presentation, re-presentation and follow-up as well as those who test positive for HIV. We describe a cohort of NPEP individuals from the commencement of the service to 31 December 2009. During this time, 1864 individuals presented for NPEP on 2396 occasions. The majority (85%) were men who have sex with men (MSM) presenting after receptive anal intercourse (56.1%). Repeat NPEP presentations were high (17.5%) and follow-up testing at week 12 post-NPEP was low (34%). Twenty-two patients (1.2%) tested positive for HIV at baseline presentation and six patients seroconverted to HIV during follow-up. The VNPEPS has initiated strategies to encourage behaviour change for those who re-present for NPEP, and to improve rates of week 12 follow-up.

Spectrum of clinical presentation, treatment and prognosis in a series of eight patients with leukaemia cutis.

All types of leukaemia can disseminate to the skin, producing cutaneous deposits known as leukaemia cutis (LC). We undertook a retrospective study to review the clinical presentations, treatment and outcome of eight patients with LC managed in our department over a period of 12 years. The clinical phenotype varied, with erythematous papules and nodules occurring with greatest frequency. Infiltrated haemorrhagic plaques and perifollicular acneiform papules were also seen. Although patients were treated aggressively for their underlying leukaemia, and received therapy directed towards LC, they tended to be refractory to treatment and the diagnosis was generally associated with a poor prognosis. The exception was a patient with chronic lymphocytic leukaemia, who survived 3 years after developing LC.

Third metacarpal bone laterality asymmetry and midshaft dimensions in Thoroughbred racehorses.

OBJECTIVE: The aims of this study were to test whether longer third metacarpal (MC3) bones had thicker dorsal cortices in a group of racehorses that were exercising at similar maximum speeds, and to establish if horses with larger differences in length between their right and left MC3 bones showed larger differences in the dorsal cortical thickness between the two limbs. DESIGN: An observational study. PROCEDURE: Forty Thoroughbred racehorses aged between 2 and 6 years and in training at racing speed at two racing stables were used. Two sets of radiographs of each left and right metacarpus of each horse were measured for bone length and dorsal cortical width according to standardised methods. RESULTS: The dorsal cortex thickness showed a linear relationship with bone length for the range of lengths between 25 and 30 cm for both the right MC3 (R2 = 0.30, P = 0.0003) and the left (R2 = 0.23, P = 0.002). The longer bones had thicker dorsal cortices. When results from the two limbs were combined to test if the difference in length between the right and left MC3 in an individual horse was associated with a thicker dorsal cortex in the longer MC3 there was no consistent relationship (R2 = 0.008, P = 0.58). CONCLUSION: In this sample of racehorses longer MC3 bones were likely to have been exposed to a greater dorsopalmar bending moment at the mid shaft that was reflected in a thicker dorsal cortex. The lack of a relationship between midshaft thickness and bone length within individual horses suggests that direct mechanical effects of conformation and environment were less important than the individual's level of skill (or the degree of laterality in their movements) developed before their exposure to fast exercise. It is likely that racehorses with longer right MC3 bones were more able to control the loading of the right MC3 than the left during fast exercise.

Lues maligna.

The incidence of syphilis in the UK is rising, particularly in HIV-positive men. We describe a Caucasian, HIV-negative woman who presented with secondary syphilis taking the form known as lues maligna. She also demonstrated the prozone phenomenon whereby the rapid plasmin reagin test was negative, but the Venereal Disease Research Laboratory and Treponema pallidum haemagglutination tests were positive.

Purpura fulminans -- a novel presentation of Churg Strauss syndrome.

Purpura fulminans is a rare syndrome of haemorrhagic necrosis of the skin and intravascular thrombosis associated with disseminated intravascular coagulopathy. It has not previously been reported as a presenting feature of Churg Strauss syndrome.

Association of human apolipoprotein E with lipoproteins secreted by transfected McA RH7777 cells.

To examine the association of apolipoprotein (apo) E with nascent hepatic lipoproteins we have prepared stable transfectants of the rat hepatoma cell line McA RH7777 expressing the human apoE3 cDNA. When the nascent lipoproteins secreted from control cells were separated on fast protein liquid chromatography (FPLC) columns, rat apoE was detected in the very low density (VLDL) and high density lipoprotein (HDL) fractions, while rat apoA-I was found in the HDL and lipoprotein free fractions. Human apoE was also associated with the VLDL and HDL particles secreted from the transfected McA RH7777 cells. Expression of human apoE resulted in a significant decrease in the amount of rat apoA-I associated with the lipoprotein particles. Rat apoE was also displaced, but to a lesser extent. Infection of McA RH7777 cells at different multiplicities of infection with recombinant adenoviral vector containing the human apoE cDNA indicated that rat apoA-I was decreased in the HDL fractions at lower levels of expression of human apoE than was rat apoE. The HDL particles were further examined by immunoblotting of nondenaturing gradient gels and by non-denaturing immunoprecipitation. The results indicate that the high density lipoprotein (HDL) particles are heterogeneous in size and apolipoprotein composition with the majority of the rat and human apolipoproteins being located on different particles. These results suggest that the profile and concentration of HDL apolipoproteins produced in hepatocytes influences the assembly of the various subsets of secreted HDL.

The significance and prevention of air emboli with the total artificial heart.

Embolism remains a significant complication of the total artificial heart (TAH). The ineffectual deairing of the TAH can allow embolization of the retained air. The standard needle aspiration of TAH air (Group A) was compared with a new protocol (Group B) that included standard needle TAH aspiration plus simultaneous pumping of the TAH against an occluded ascending aorta and main pulmonary artery with vacuum applied to a needle in the proximal aorta and pulmonary artery. There were 4 calves in each group. There was no premortem evidence of systemic or pulmonary emboli. Both groups of animals were electively terminated less than 2 weeks postoperatively Postoperative mean aortic and pulmonary artery pressures were recorded for each animal. Animals in Group B had a significant decline in pulmonary artery pressures (43 +/- 12 vs. 33 +/- 8 mm Hg) 1 h after TAH implantation when compared with Group A. All other aortic and pulmonary artery pressure differences between Groups A and B were not statistically significant within 24 h of the operation. Group A animals had a 75% incidence, and Group B animals had 100% incidence of TAH thrombus. This very small thrombus was found exclusively at the inflow valve-TAH housing interface. Evaluation of the kidneys postmortem was used to identify embolic injury. All animals in Group A had evidence of acute, hemorrhagic injury, but none of the Group B animals had similar injury. Half of the animals in each group had small, fibrotic chronic renal cortical injury, which did not develop during TAH implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Remnant atrial function in human and animal recipients of a total artificial heart.

The native atria remains intact after total artificial heart (TAH) implantation. The electrical activity of the recipient's atria can be recorded from wires placed during TAH implantation. Regulating TAH heart rate by coupling it with native atrial activity has the potential for a more physiologically responsive TAH. The reactivity of the atrial impulse rate is a critical component of this link, but little is known about atrial responsiveness after TAH placement. Two human and three animal TAH recipients had recordable atrial electrical activity. Human atrial impulse rate after TAH was relatively constant at rest but unresponsive to physiologic stimuli. Analysis of human atrial contraction provided no discernable effect on ventricular filling. Animal atrial impulse rate at rest was more rapid than calves without a TAH. The bovine TAH recipients had an atrial impulse rate that responded to catecholamine stimulation and blockade. Isoproterenol caused a significant rise in atrial impulse rate (152 +/- 16 impulses per minute to 216 +/- 24 impulses per minute; p < 0.05) and propranolol caused a decrease in atrial impulse rate (142 +/- 20 impulses per minute to 122 +/- 19 impulses per minute; p > 0.05). Despite beta blockade, the atrial impulse rate remained abnormally elevated secondary to unknown factors. Animal atrial contraction did appear to intermittently augment TAH ventricular filling. These data indicate that the atria remains electrically intact after TAH implantation. The human atrial impulse rate was unresponsive to physiologic stimuli although the animal atrial impulse rate was affected by exogenous catecholamine administration, but the rate remained abnormally rapid.(ABSTRACT TRUNCATED AT 250 WORDS)

Permanent pacing in heart transplant recipients: underlying causes and long-term results.

Although the majority of heart transplant recipients have a satisfactory heart rate, a substantial number require a permanent pacemaker. In 7 of 46 heart transplant patients at our institution symptomatic bradycardia developed, necessitating implantation of a transvenous pacemaker. The average time from heart transplantation to pacer insertion was 25 days. The average donor age, ischemic period, and crossclamp time was 28 years, 182 minutes, and 113 minutes, respectively. A long aortic crossclamp time (greater than 83 minutes) increased the risk for conduction abnormalities in the sinoatrial node. No patient had rejection before the pacer implantation. Five of the seven patients continue to be paced a significant amount of a 24-hour period. Only one patient has had considerable improvement in 3 years, requiring pacing only 3% of a monitored 24-hour period. This patient had the longest ischemic time and the most rejection episodes after implantation of the pacemaker. One patient was paced 100% until a second heart transplantation was done, without a subsequent need for pacing. The other five patients' hearts continue to be paced between 80% and 100% of a 24-hour monitored period. The donor intrinsic heart rates of these five patients produce symptomatic bradycardia. The success of AAI pacing in all patients indicates normal conduction below the sinoatrial node. The injury or dysfunction resulting in bradycardia was isolated to the sinoatrial node. Long-term follow-up in three patients (greater than 3 years) shows the need for pacing to be intermittent but long term. Most patients never fully recover from symptomatic bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine increases cardiac output of the total artificial heart. Implications for vascular contribution of inotropic agents to augmented ventricular function.

BACKGROUND: The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha- and beta-adrenergic agonist activity. METHODS AND RESULTS: To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p less than 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p less than 0.005) with dobutamine administration. CONCLUSIONS: These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility.

Adenine nucleotide content in cold preserved human donor hearts and subsequent cardiac performance after orthotopic heart transplantation.

Myocardial high-energy phosphate content has been used as a parameter to evaluate the adequacy of donor organ preservation. The purpose of this study was to assess current techniques of preservation by measuring high-energy phosphates in cold preserved (4 degrees C) human donor hearts. Endomyocardial biopsy samples of the donor heart right ventricular septum (n = 24) were compared with samples from patients with normal cardiac function evaluated before chemotherapy (n = 12). Left ventricular and right ventricular ejection fractions were measured by means of radionuclide angiography early (24 to 72 hours) and late (mean 42 days) postoperatively. Mean total cold ischemic time was 146 +/- 54 minutes (range, 89 to 340 minutes). ATP nmol/mg noncollagenous protein in donor hearts was 38.2 +/- 10.7 and 31.9 +/- 13.6 (p = NS) in normal hearts. Early postoperative left ventricular and right ventricular ejection fraction was 55% +/- 14% and 40% +/- 9%, respectively. Late postoperative left ventricular and right ventricular ejection fraction was 64% +/- 14% and 50% +/- 10%, respectively; both represent significant increases in right and left ventricular ejection fraction (p less than 0.05). No correlation was found between ischemic time and donor ATP, ischemic time and ejection fraction, or ejection fraction and ATP. Three patients with normal donor heart ATP content had severe, but reversible, early graft dysfunction. In summary, currently used human donor heart preservation techniques are associated with normal values of high-energy phosphates and usually excellent early and late postoperative graft function.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals.

Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes. A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues. The skin button is designed to protect the tissues from damage and provide a secure material-tissue interface. Prevention of superficial and invasive infection is the primary goal of the skin button. Eight calves were studied prospectively to identify gross or microscopic infection with the skin button. All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection. All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation. No animal died secondary to a skin button infection. Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects.

Effect of a total artificial heart on adaptive hormonal responses in humans with end-stage heart failure.

The J-7 total artificial heart (TAH) can restore normal vascular hemodynamics in humans treated for end-stage heart failure, but less is known regarding its effect on hormones elevated under these conditions. A 49-year-old man with NYHA Class IV end-stage heart failure received a J-7-70 TAH as a bridge to transplantation. Pre-TAH cardiac index was less than 2 L/min/m2 with end organ dysfunction, increased venous and pulmonary pressures, and a low arterial pressure. The TAH provided an immediate cardiac index greater than 3 L/min/m2 with normal hemodynamics and organ function. Pre-TAH renin, aldosterone, and atrial natriuretic factor (ANF) levels were markedly elevated: 147 ng/dl, 29.4 ng/dl, and 380 pg/ml, respectively. All values declined dramatically by the fifth postoperative day, with the aldosterone and ANF values returning to normal at 11.5 ng/dl and 37 pg/ml, respectively. Renin levels reached normal values by the fourth postoperative week. Once normal values were obtained, they remained in this range for the 57 days of TAH function. The TAH, used in end-stage heart failure, restores normal hemodynamics and compensatory hormonal levels. These hormones can be used as indicators of proper TAH function in such patients.

The role of beta receptors in the peripheral vasculature of calves with a total artificial heart.

Drugs given to a total artificial heart (TAH) calf isolate their vascular effects independent of the myocardium. During experiments, the TAH maintains full ejection, constant heart rate, and percent systole, and uses no vacuum. Cardiac output (CO) varies solely and directly with preload. Six calves received an infusion of isoproterenol, a beta agonist, and three calves received propranolol, a beta antagonist. The isoproterenol was resumed after beta blockade. Isoproterenol alone caused a significant increase in CO, an effect that was attenuated but not eliminated with beta blockade. Both isoproterenol and propranolol decreased AoP, but only isoproterenol increased preload. Beta receptors play a significant role in decreasing venous capacitance with increased preload and CO, independent of the myocardium.