EMPACT syndrome

Background: Seizure prophylaxis with phenytoin is a common measure in oncologic patients with brain metastases. In these patients, generalized severe adverse drug reactions such as erythema multiforme (EEM) may occur. However, in a subgroup of patients with brain radiation therapy, EEM‐like lesions develop particularly in the radiation field. Most recently, the acronym EMPACT ( E rythema M ultiforme associated with P henytoin A nd C ranial radiation T herapy) was proposed to specifically describe this syndrome. Patient/Method: Here, we report on EMPACT syndrome in a 46‐year‐old woman. Therapeutic measures included seizure prophylaxis with phenytoin and total brain radiation therapy of brain metastases from bronchial carcinoma. Three weeks after introduction of phenytoin, the patient presented with EEM‐like skin lesions restricted to the original radiation field and facial mucocutaneous involvement. After a few days, the rash spread to the upper part of the body. She was also in poor general condition. Results: The immediate cessation of phenytoin therapy, combined with administration of systemic corticosteroids and high dose immunoglobulins along with intensive local treatment and pain medications, resulted in complete resolution of the skin eruption. Patch testing to phenytoin was positive after 72 hours. Conclusion: EMPACT should be classified as an specific entity among the EEM‐like drug reactions as it only appears after radiotherapy and seizure prophylaxis with the anticonvulsant phenytoin. We propose including specific type IV‐sensitization to phenytoin into the definition of EMPACT.     

Exogenous Modulation of TGF-β1 Influences TGF-βR-III-Associated Vascularization during Wound Healing in Irradiated Tissue

BACKGROUND AND PURPOSE: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)beta isoforms following surgery in irradiated graft beds. Altered levels of TGF-beta(1) are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-beta receptor-III (TGF-betaR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-beta(1) treatment on TGF-betaR-III-associated vascularization in the transition area between irradiated graft bed and graft. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n = 16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 micro g anti-TGF-beta(1) into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-betaR-III and E-selectin expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. RESULTS: A significantly higher expression of TGF-betaR-III was seen in the irradiated and anti-TGF-beta(1)-treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-betaR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-beta(1)-treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher in the TGF-beta(1)-treated group. CONCLUSION: Neutralizing of TGF-beta(1) activity in irradiated tissue undergoing surgery leads to a higher expression of TGF-betaR-III and increased vascularization. TGF-betaR-III seems to be associated with newly formed blood vessels during neovascularization in wound healing.     

Keratoacanthoma-Like Squamous Cell Carcinoma Within the Fibroepithelial Polyp

Acrochordons (skin tags) are often considered clinically insignificant cutaneous redundancies that should be removed and destroyed with no histopathologic analysis performed. One rarely finds another neoplasm within an acrochordon. We describe a patient with an acrochordon that contained a squamous cell carcinoma that had features resembling a keratoacanthoma. This is the first time to our knowledge that an invasive squamous cell carcinoma has been described within an acrochordon.     

Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles

The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo , and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively.     

Die doppler-sonographische beurteilung der funktionsfähigkeit extra-intracranieller anastomosen

Zusammenfassung Wir berichten fiber die Doppler-sonographischen Ergebnisse bei 33 Patienten mit einer Anastomose zwischen der A. temporalis superficialis and der A. cerebri media. Die Indikation zur Bypass-Operation beinhaltete rezidivierende TIA oder ein kurz zuvor erworbenes leichtes neurologisches Defizit bei angiographischem Nachweis einseitiger oder beidseitiger tiefer Obliterationen der A. carotis interna und hochgradiger Stenosen oder Verschlüsse im distalen Abschnitt der A. carotis interna bzw. im proximalen Abschnitt der A. cerebri media. Die Funktionsfahigkeit der Anastomose wurde überpriift durch die Berechnung der modifizier ten Pourcelot-Indices (relative enddiastolische Strömungsgeschwindigkeit) der A. temporalis superficialis praeauriculär und am Bohrlochrand Bowie durch den EinfluB der intermittierenden Kompression des den Bypass-versorgenden Gefäßes auf den modifizierten Pourcelot-Index der ipsilateralen A. carotis communis. Bei allen Patienten mit funktionsfahigen Anastomosen, definiert durch einen modifizierten Pourcelot-Index von zumindest 0,20 am Bohrlochrand, kam es zu einer Reduktion dieses Parameters um durchschnittlich 0,08 an der A. carotis communis bei kurzfristiger Kompression des den Bypass-versorgenden Astes. Bei den 18 Patienten mit unilateraler Obliteration der A. carotis interna war der Bypass über-wiegend dann funktionsfähig, wenn die summierten modifizierten Pourcelot-Indices der verbliebenen hirnversorgenden Gefäße um zumindest 10% gegenüber einem vergleichbaren Normalkollektiv reduziert waren. Das Vorhandensein bzw. das Fehlen von Ophthalmica-Kollateralen hatte dabei keinen Einfluß auf den Prozentsatz der funktionsfahigen Anastomosen in diesen Untergruppen. Bei den vier Patienten mit bilateraler Obliteration der A. carotis interna war die angelegte Anastomose in jedem Fall funktionsfähig, während die Hälfte der Patienten mit Stenosen and Verschlüssen im distalen Abschnitt der Carotisstrombahn nur eine ungeniigende Bypass-Funktion zeigten. Die zwei Patienten mit einer Mediahauptstammstenose bzw. -obliteration hatten Indices von 0,45 bzw. 0,46 am Bohrlochrand als Hinweis auf die Funktionstüchtigkeit. Wir Bind der Auffassung, daß man mittels Doppler-sonographischer Kriterien die Funktionsfahigkeit einer Temporalis superficialis-Cerebri media-Anastomose überprüfen kann. Der praeoperativ berechnete summierte modifizierte Pourcelot-Index der verbliebenen hirnversorgenden Arterien kann zumindest bei uni- and bilateraler Internaobliteration als zusatzlicher Parameter herangezogen werden, um die Indikation zur Bypass-Operation zu klären.     

Documentation of students' clinical reasoning using a computer simulation

Computer simulations can provide both a clinical experience for teaching problem solving and a method of documenting a student's clinical reasoning style. The CAMPS simulation consists of approximately 500 items describing a patient's history, physical examination and laboratory results, and treatments. The student has full option to select any item in any order, producing a wide variation of performances. Since all of the students interact with the same clinical problems, the faculty member can make comparisons of that individual student with the class. From the record of the simulation encounter, the person responsible for student evaluations can prepare a narrative that lists the overall performance, the specific omissions and commissions, and comparisons with the class. Experience with a group of 111 students in a basic pediatric course showed that this method of documenting clinical inquiry detected a variety of levels of performances. Comparisons of the results of these tests with the faculty observations showed that 16% of these students who were judged to be very good or excellent in problem solving by the faculty performed at least 1 SD below the class average on the simulations. This project highlights the power of computer simulations to provide documentation of student performance with the additional benefit of a cost of less than $1 per student.     

Steady state verapamil tissue distribution in the dog: differing tissue accumulation

Plasma, heart, and extracardiac tissue verapamil concentrations were measured after sustained intravenous infusions in 11 dogs to determine the differential tissue accumulation of verapamil. A steady state verapamil concentration of 327 +/- 50 ng/ml decreased the mean arterial blood pressure from 104 +/- 9 to 90 +/- 6 mm Hg (p = 0.08) and the P-R interval increased from 118 +/- 4 to 176 +/- 13 ms (p less than 0.001) with second-degree atrioventricular block developing in 6 animals. Verapamil accumulated in organs in the following order: Lung much greater than kidney greater than spleen greater than ventricular myocardium = liver greater than atrial myocardium greater than cerebral cortex greater than fat = skeletal muscle. Levels in the ventricular free wall were consistently greater than atrial levels, but no difference was observed between left versus right-sided cardiac chambers. In summary, affinity of different organs for verapamil is highly variable and organ-specific; furthermore, differential intracardiac chamber accumulation occurs.     

Dynamic pituitary and ovarian changes occurring during the anestrus to estrus transition in the golden hamster

Anestrous hamsters exhibit daily afternoon gonadotropin and progesterone surges, but little estrogen secretion. In the first experiment, short day anestrous females were transferred to long days to detect hormonal changes associated with recovery of cyclicity. Morning and afternoon blood samples were taken at increasing durations in long days. Females autopsied at their first vaginal estrus after transfer to long days differed from long day estrous controls only in their lower uterine weights. Some females at all durations exhibited signs of recovery, though they had not yet shown estrus. They did not display afternoon gonadotropin surges and had low circulating progesterone but high estradiol levels, stimulated uteri, and enhanced follicular development. Results of the second and third experiments provided evidence that the daily gonadotropin surges are not the cause per se of anestrus, and that changes in estrogen secretion are essential for the transition to and from anestrus. Phenobarbital blockade of the daily surges in anestrous females did not result in increased follicular growth and estrogen secretion. Furthermore, daily afternoon injections of gonadotropins it appears that the daily surges in anestrous hamsters simply reflect low estradiol levels. It is still not known what signal promotes rapid follicular maturation during the recovery from anestrus. Once initiated, however, this recovery appears to occur within a few days, with a rapid cascade of events. First, follicular development and estrogen secretion resume, and the daily LH surges cease. Then, progesterone levels decline, and an ovulatory surge of gonadotropins is triggered.