[Eruptive epidermoid cysts during topical imiquimod treatment]. / Éruption de kystes épidermiques après application d'imiquimod topique.

BACKGROUND: Imiquimod is a local immune-response modifier that works by stimulating innate and acquired immunity. It is frequently used to treat superficial basal cell carcinoma, the most common form of skin cancer. Marked local inflammatory reaction is common during treatment. We report a case of the rare condition, multiple eruptive milia, during topical imiquimod therapy. PATIENTS AND METHODS: A 67-year-old male patient presented infiltrating basal cell carcinoma above the left eyebrow. The patient underwent surgery and skin grafting. He presented superficial relapse at the periphery of the graft and was initially treated with Aldara®. Fifteen days after initiation, Aldara® was withdrawn due to a critical inflammatory reaction. A few weeks after complete healing, an erythematous annular plaque of milia, excluding the graft zone, appeared. This element was confirmed by histopathology. DISCUSSION: The most common local side effects reported with Aldara® are erythema, irritation and crusting. Reports of eruptive milia following Aldara® therapy are rare and they are never mentioned in the summary of product characteristics. Application of imiquimod in fact induces local inflammatory reaction due to stimulation of local cytokines, which can result in marked reaction in the infundibular epithelium of hair follicles and thus in the production of abnormal keratin that can cause pilosebaceous duct obstruction and thus the formation of epidermoid cysts. This pathological mechanism explains the absence of lesions on the skin graft of the inner arm. CONCLUSION: The occurrence of eruptive milia during treatment with Aldara® is rarely described. The timing of occurrence of these eruptive milia as well as the mechanism of action of the drug made such a reaction highly probable in our patient.

Survival control of malignant lymphocytes by anti-apoptotic MCL-1.

Programmed apoptotic cell death is critical to maintain tissue homeostasis and cellular integrity in the lymphatic system. Accordingly, the evasion of apoptosis is a critical milestone for the transformation of lymphocytes on their way to becoming overt lymphomas. The anti-apoptotic BCL-2 family proteins are pivotal regulators of the mitochondrial apoptotic pathway and genetic aberrations in these genes are associated with lymphomagenesis and chemotherapeutic resistance. Pharmacological targeting of BCL-2 is highly effective in certain indolent B-cell lymphomas; however, recent evidence highlights a critical role for the BCL-2 family member MCL-1 in several lymphoma subtypes. MCL-1 is recurrently highly expressed in various kinds of cancer including non-Hodgkin's lymphoma of B- and T-cell origin. Moreover, both indolent and aggressive forms of lymphoma require MCL-1 for lymphomagenesis and for their continued survival. This review summarizes the role of MCL-1 in B- and T-cell lymphoma and discusses its potential as a therapeutic target.

Re-activation of mitochondrial apoptosis inhibits T-cell lymphoma survival and treatment resistance.

T lymphocyte non-Hodgkin's lymphoma (T-NHL) represents an aggressive and largely therapy-resistant subtype of lymphoid malignancies. As deregulated apoptosis is a frequent hallmark of lymphomagenesis, we analyzed gene expression profiles and protein levels of primary human T-NHL samples for various apoptotic regulators. We identified the apoptotic regulator MCL-1 as the only pro-survival BCL-2 family member to be highly expressed throughout all human T-NHL subtypes. Functional validation of pro-survival protein members of the BCL-2 family in two independent T-NHL mouse models identified that the partial loss of Mcl-1 significantly delayed T-NHL development in vivo. Moreover, the inducible reduction of MCL-1 protein levels in lymphoma-burdened mice severely impaired the continued survival of T-NHL cells, increased their susceptibility to chemotherapeutics and delayed lymphoma progression. Lymphoma viability remained unaffected by the genetic deletion or pharmacological inhibition of all alternative BCL-2 family members. Consistent with a therapeutic window for MCL-1 treatment within the context of the whole organism, we observed an only minimal toxicity after systemic heterozygous loss of Mcl-1 in vivo. We conclude that re-activation of mitochondrial apoptosis by blockade of MCL-1 represents a promising therapeutic strategy to treat T-cell lymphoma.

Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma.

Medallion-like dermal dendrocyte hamartoma is a newly described and rare clinical and pathological entity. This congenital, round, erythematous and atrophic lesion in the thoracic area is histologically characterized by a CD34+ dermal and hypodermal spindle-cell infiltration. We describe the clinical, histopathological, cytological and molecular features of three cases of dermal dendrocyte hamartoma. In all the cases, atrophic congenital dermatofibrosarcoma protuberans (DFSP) was the first histological diagnosis. In one case, wide surgery had been performed on the basis of the clinical and histological presentation. The histological pattern was similar in all the cases: epidermal atrophy and a spindle to ovoid cell proliferation in the dermis and in the subcutaneous fat. Immunochemical staining for CD34 and factor XIIIa was positive. Cytogenetic and molecular studies were performed; no chromosomal abnormality nor translocation t(17;22)(q22;q13) was observed. Fluorescence in situ hybridization analysis did not reveal the DFSP fusion gene COL1A1-PDGFB. We observed that the main diagnostic pitfall of medallion-like dermal dendrocyte hamartoma is atrophic congenital DFSP due to clinical and histological similarities. We emphasize that molecular studies to eliminate the t(17;22)(q22;q13) translocation of DFSP may provide determinant elements for diagnosis in order to avoid unnecessary mutilating surgery.

Earlier discharge of infants from neonatal intensive care units: a pilot program of specialized case management and home care. Delaware Valley Child Health Alliance.

A multidisciplinary approach using a neonatology independent physicians association, affiliated hospitals, a pediatric home care company, and a health maintenance organization was designed to promote earlier safe discharge of infants from intensive care. This pilot project involved 43 infants who received case management and early discharge home with home oxygen, monitoring, intravenous antibiotics, gavage feedings, phototherapy, or nutritional management for poor weight gain. A staff neonatologist remained the primary physician until the patient would have been discharged according to standard criteria. Two patients had unscheduled readmissions and all infants survived. This approach resulted in an estimated savings of 456 hospital days and $329,982; 89% of parents rated the care as good to excellent, and 83% were satisfied with the program and outcome. This study suggests that a prospectively designed program can be designed to promote safe earlier discharge of infants in intensive care.

Skin-to-skin parental contact with fragile preterm infants.

Skin-to-skin contact has been implemented recently to facilitate maternal-infant bonding of preterm infants. The technique allows the removal of fragile preterm infants from an incubator to the bare chest of a parent or caretaker. When specific guidelines are followed, thermal stability can be maintained, parent-infant bonding can be facilitated, and parental satisfaction can be enhanced. We illustrate a case in which a preterm infant has skin-to-skin contact while being monitored for physiologic parameters, including heart and respiratory rate, oxyhemoglobin saturation, and nasal airflow. Improvements in breathing patterns in this infant during skin-to-skin care and maintenance of a normal temperature suggest that this technique may not only be safe and psychologically beneficial, but it may also promote physiologic improvement.

Partial liquid ventilation in critically ill infants receiving extracorporeal life support. Philadelphia Liquid Ventilation Consortium.

OBJECTIVES: To demonstrate that a period of partial liquid ventilation (PLV) with perflubron improves pulmonary function, without adverse events, in a select group of critically ill infants receiving extracorporeal life support (ECLS) with a high likelihood of mortality. METHODS: This was an open-label, noncontrolled, phase I and II trial of PLV in two infants with congenital diaphragmatic hernia and four infants with acute respiratory distress syndrome (ARDS) who were failing to improve while receiving ECLS. PLV was performed by instilling and maintaining a functional residual capacity of sterile perflubron for 4 to 96 hours. RESULTS: Four infants were successfully weaned off ECLS for at least 3 days, and two infants (both with ARDS) are long-term survivors after PLV. All infants demonstrated lung recruitment and improved lung compliance, and there were no adverse events related to PLV. CONCLUSIONS: The study suggests that perflubron PLV is safe, improves lung function, and recruits lung volume in critically ill infants receiving ECLS. PLV therapy for infants with ARDS seems to have a great deal of promise. Based on this and other phase I and II trials, studies of PLV on selected full-term infants before ECLS have been initiated.

Documented home apnea monitoring: effect on compliance, duration of monitoring, and validation of alarm reporting.

The objectives of this study were to: (1) measure patient compliance with monitoring, (2) validate parental reports of alarms at home, (3) examine monitoring duration, and (4) compare documented monitor records with the traditional pneumogram to evaluate patients for monitor discontinuation. During the 1-year period from January through December, 1992, 114 infants were followed up with documented monitoring. Simultaneously, 113 infants were followed up with conventional monitors. Infants were premature, or victims of apparent life-threatening episodes (ALTE), or siblings of SIDS victims. Monitors recorded all episodes of apnea greater than 15 seconds and bradycardia less than 80 beats per minute. All families were contacted biweekly by telephone. Downloads were performed at regular intervals. Monitor downloads were compared with simultaneous pneumograms to assess the accuracy of a long-term, intermittent event-recording system versus short-term (6- to 12-hour) continuous recording. All families were highly compliant with the use of home monitoring. Although Caucasian families used the monitors more often than non-Caucasian families, all groups used the monitor > 75% of the time. True episodes were verified in 38% of patients by monitor downloads. Only 7.4% of all recorded events were true events. Of the real events, 51.2% were apneas of 16-20 seconds. No significant differences were found in overall duration of monitoring between documented and nondocumented monitors. In the premature infants, the duration of monitoring was significantly reduced in those infants found to have no true episodes over those with real events at home. Readmission for ALTE was reduced in infants with documented monitors. Premature infants without events were monitored an average of 24 fewer days (P = 0.03). Computerized monitor downloads were found to be equally, if not more, sensitive than pneumograms in evaluating infants for monitor discontinuation. Documented monitoring offers a viable alternative to traditional monitoring and pneumograms in assisting clinicians and families in evaluating their infant's progress. By accurately assessing compliance, distinguishing true from false alarms, and decreasing the need for pneumograms, these devices provide valuable information to clinicians and families.

Recent advances in home infant apnea monitoring.

Appropriate and effective nursing intervention is an essential element in determining how the family responds to the monitor in the home. Accurate assessment of the family system and dynamics provides the basis for a plan of care. The family's and infant's specific needs must be addressed. Careful implementation of the plan allows for changes and unexpected outcomes. Frequent evaluation of monitoring is necessary to determine if a change in the plan of care is needed. Recent changes in home apnea monitoring technology are rapidly altering the care of infants at risk for apnea and SIDS. The advent of the documented or recording monitor has the potential to demystify the events occurring while the infant is being monitored. Parents can get answers about their infant as quickly as a telephone call. The clinician can differentiate between a true and a false alarm and reassure the parents accordingly. Documenting false events and shallow-breathing alarms will potentially reduce the duration of monitoring, decreasing costs to the entire health care system. Documented monitoring is a valuable tool for nurses. For the staff nurse, clinical observation can be validated through trending and print out of events can be done at the bedside. For the advanced practice nurse, management of care can become more efficient through remote monitoring via modem. Patient teaching can be followed with immediate feedback. Monitors may assist in allaying anxiety in families who have lost children to SIDS or had an unexpected death in a previous sibling. Families may feel less anxious about having an "at risk" child in the home if the events are continuously being recorded. Length of hospital stay may decrease initially, with fewer rehospitalizations. Nursing research in these areas is necessary. Evaluating events occurring in the home may also help shed light on the enigma of SIDS. Several SIDS deaths have been recorded on documented monitors. If we can pinpoint exactly what takes place prior to and immediately after a SIDS episode, the enigma that has had physicians puzzled for so long may finally begin to unravel.

Infant sleep position following new AAP guidelines. American Academy of Pediatrics.

OBJECTIVE: This report examines the response of families to the American Academy of Pediatrics June 1992 recommendation that healthy term infants be put to sleep on their back or side to decrease the risk of sudden infant death syndrome. Parents at two clinics and private practices were interviewed to ascertain sleep position practices. METHODS: Parents of infants from 1 to 6 months of age who were in the waiting room for a well-child visit were eligible for study. A total of 760 interviews were conducted using a closed-ended questionnaire. Parents were asked about sleep position, positional changes during sleep, and factors that influenced their decision to position their infant prone, side, or supine. Interviews were conducted from September 1993 through April 1994. This interval was divided into two equal, 4-month time intervals. Sleep practices were compared during the first and second time periods. Differences between practice and clinic groups were measured. Groups were compared using the chi-square test, with results considered significant at P < .05. RESULTS: The number of infants placed side or supine for sleep increased significantly since the inception of the study, from 38.1% to 59.1%. Despite this increase, parents reported that the impetus for changing position came from family or the media, rather than from health professionals. Initially, the proportion of infants in private practices placed side or supine was greater than that of clinic patients. That difference disappeared by the end of the study. Prone positioning continued to be more prevalent in the 3- to 6-month-old infants than in the 1- to 3-month-old group. The majority of infants at all ages awoke in the same position that they were put to sleep. CONCLUSIONS: Side and supine positioning for sleep increased in all socioeconomic groups. A small number of infants placed side or supine for sleep are found prone on awakening. Health professionals need to increase their role in providing sleep position guidance. As the proportion of the population positioning their infants side or supine for sleep increases, it should be possible to examine the effect on the sudden infant death syndrome rate.

Lisfranc's fracture-dislocation. An unusual case presentation.

The authors present a brief review of the literature with an unusual case presentation of Lisfranc's dislocation. The authors review the mechanism of injury, presentation, and treatment alternatives for both acute trauma-related injuries and neuropathic-related injuries to the Lisfranc's joint. The authors discuss the controversy surrounding the preferred treatment of neuropathic-associated injuries and suggest that possibly criteria may be established for fusion versus conservative care of these injuries.

Leech therapy: new procedures for an old treatment.

Experiences of pediatric ICU nurses as they cared for a child requiring leech therapy are described in this article along with the clinical conditions and therapy of the case. The nurses' ambivalence about participating in what seemed to be an archaic therapy and how they had to put such feelings aside to support the family are explained.

Protein disulfide isomerase appears necessary to maintain the catalytically active structure of the microsomal triglyceride transfer protein.

Protein disulfide isomerase (PDI) is a component of the microsomal triglyceride transfer protein (MTP) complex. This study was initiated to help elucidate the role of PDI in MTP. The 88-kDa polypeptide of MTP (88K) was dissociated from PDI by using chaotropic agents (NaClO4 and KSCN), low concentrations of a denaturant (guanidine hydrochloride) or a nondenaturing detergent (octyl glucoside). As assessed by fluorescence and circular dichroism spectroscopy, these three different approaches appeared to dissociate the components of MTP under mild, nondenaturing conditions. The dissociating agents were diluted or removed by dialysis, and the free PDI and 88K were further characterized. In all cases, the dissociation coincided with the loss of triglyceride transfer activity. The free 88-kDa polypeptide readily aggregated, suggesting that it is a hydrophobic peptide. Even in the presence of chaotropic agents, when 88K was not aggregated, transfer activity was not expressed. These results suggest that the association of PDI with 88K is necessary to maintain the catalytically active form of the triglyceride transfer protein and prevent the aggregation of 88K.

Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex.

A bovine liver protein which catalyzes the transfer of triglyceride between membranes has previously been isolated from the lumen of the microsomal fraction. When further purified about 100-fold, two polypeptides of molecular mass 58,000 and 88,000 were identified (Wetterau, J. R., and Zilversmit, D. B. (1985) Chem. Phys. Lipids 38, 205-222). We demonstrate here that the two polypeptides (referred to as 58-kDa and 88-kDa, respectively) are associated in a protein-protein complex, and that the triglyceride transfer activity is associated with this complex. Antibodies specific for either polypeptide immunoprecipitated both the 58-kDa and 88-kDa polypeptides as well as the lipid transfer activity. The 58-kDa subunit of the microsomal transfer protein complex was identified as protein disulfide-isomerase (PDI) (EC 5.3.4.1) by 1) a comparison of the amino-terminal sequence of PDI and the 58-kDa subunit of the transfer protein, 2) a comparison of the reverse phase high performance liquid chromatography peptide maps of CNBr digests of PDI and the lipid transfer protein, 3) immunoprecipitation competition experiments in which PDI was found to compete with the lipid transfer protein for immunoprecipitation by the anti-58-kDa polyclonal antibodies, 4) immunological cross-reactivity of the microsomal triglyceride transfer protein complex with polyclonal antibodies raised against PDI, and 5) the appearance of protein disulfide isomerase activity following the dissociation of purified microsomal transfer protein complex with guanidine HCl. In conclusion, the microsomal triglyceride transfer protein has a multi-subunit structure which is unique compared to other intracellular lipid transfer proteins which have been described to be single polypeptides. The unexpected finding that PDI is a component of the microsomal triglyceride transfer protein complex suggests a new previously undescribed role for protein disulfide isomerase.

Criteria for combined procedure selection in the surgical correction of the acquired flatfoot.

Surgical correction of the flexible acquired flatfoot has long been subject to procedures based on an unsound understanding of the true pathomechanics of the deformity. With the advent of modern biomechanics and the concept of planal dominance, procedure selection can become a more exacting science. A classification system based on the progression of symptoms, used in concert with a firm understanding of the primary and compensatory deformities can simplify the process of selecting combined procedures to deal with a particular foot type.

A comparative analysis of conservative versus surgical treatment of Morton's neuroma.

The authors present a study of the treatment of Morton's neuroma. Sixty patients, involving 65 feet treated, were studied. Conservative treatments were compared to surgical excision of the neuroma. As a result of the findings in this study, the authors recommend surgical excision as the initial treatment of choice.

A hirudin catching ELISA for quantitating the anticoagulant in biological fluids.

A catching ELISA has been developed that permits a quantitation of the anticoagulant hirudin in buffer, urine and plasma. In plasma hirudin can be determined in concentrations ranging from 0.2 to 25 ng/ml (2.4 X 10(-3) to 0.3 AT-U/ml), in urine between 0.8 and 200 ng/ml (0.01 and 2.4 AT-U/ml). The enzyme immunoassay allows a rapid, sensitive and reproducible quantitation of hirudin, and can thus be used to assess the pharmacokinetics of the anticoagulant in patients after parenteral and/or topic administration.

Preoperative criteria for hallux valgus surgery and use of convergent angled base wedge osteotomy.

A discussion is presented about objective correction criteria for hallux abducto valgus surgery. A historical review of commonly used procedures performed for correction at various levels of first ray deformity is related. Based on ideal criteria for base wedge osteotomies, a new template and procedure for base wedge osteotomies derived from computer-augmented graphics is described in detail. This procedure has been referred to as a convergent angled osteotomy (CAO) and effectively reduces the metatarsus primus adductus angle with minimal loss of length, cortex to cortex apposition in closure, relative lengthening with plantarflexion if desired, and a capacity for very stable rigid internal fixation that optimizes recovery from base wedge reduction. Case histories are also presented.