Taxanes-induced cutaneous eruption: another histopathologic mimicker of malignancy.

BACKGROUND: Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation. OBJECTIVES: We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically. METHODS: Cutaneous biopsies were obtained in each patient. RESULTS: Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case. DISCUSSION: These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported. CONCLUSION: Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.

Effectiveness of egg yolk immunoglobulin against the intracellular salmonid pathogen Piscirickettsia salmonis.

AIMS: To produce and characterize egg yolk immunoglobulin (IgY) against the fish intracellular pathogen Piscirickettsia salmonis as well as to evaluate the antibacterial activity of IgY in vitro and the availability in the serum of fish immunized orally. METHODS AND RESULTS: Specific IgY was produced by immunizing hens with P. salmonis proteins. The IgY was obtained from egg yolks using the ammonium sulphate precipitation method and it was characterized by SDS-PAGE, Western-blot and ELISA, demonstrating that anti-P. salmonis IgY strongly reacted specifically against P. salmonis proteins. In an in vitro neutralization assay, IgY inhibited the growth of P. salmonis in liquid medium at concentrations ranging from 128 to 256 µg ml(-1) in a dose-dependent manner. Interestingly, IgY against P. salmonis also generates a strong protective effect on the infection of P. salmonis in salmon head kidney-1 cells. In addition, the bacteriostatic function of IgY appears to result possibly from agglutination by the interaction of IgY with surface components of the pathogen. Finally, to confirm this IgY as an alternative for salmonid treatment, Atlantic salmon (Salmo salar) specimens were orally inoculated with IgY. The analysis of the sera demonstrates that IgY was effectively transported by fish intestine and that this immunoglobulins maintains its properties and recognizes several proteins of P. salmonis up to 12 h after inoculation of IgY against P. salmonis. CONCLUSIONS: Specific IgY effectively inhibited the growth of P. salmonis and this immunoglobulin can be released in the Atlantic salmon sera when administered orally to fish. SIGNIFICANCE AND IMPACT OF THE STUDY: We propose that this specific IgY against this fastidious micro-organism could be a useful strategy for the treatment of piscirickettsiosis.

Amyophatic dermatomyositis presenting as a flagellated skin eruption with positive MDA5 antibodies and thyroid cancer: a real association?

Amyopathic dermatomyositis (ADM) is characterized clinically by typical skin lesions with hypomyopathy or no muscular involvement. ADM has been recently reported to be complicated by rapidly progressive interstitial lung disease (ILD), especially in patients with positive antibodies against melanoma differentiation-associated gene 5 (MDA5). These patients may have a low risk of cancer, but no clinical, histological or laboratory markers completely specific for paraneoplastic DM have been identified to date. We report a case of flagellate erythema as the initial presentation of ADM associated with ILD, positive MDA5 antibodies and a concomitant diagnosis of thyroid cancer. We discuss the unusual clinical features and associations that make this case particularly interesting.

Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis.

BACKGROUND AND OBJECTIVE: Peptidoglycan (PGN) and lipopolysaccharide (LPS) are bacterial cell wall constituents that are able to induce bone resorption by stimulating Toll-like receptor (TLR) 2 and TLR4, respectively. The fragments of PGN also stimulate inflammatory responses via nucleotide-binding oligomerization domain (NOD) 1 and NOD2, although there are differences in the NOD-stimulatory activities between gram-positive and gram-negative PGNs. The TLR and NOD signaling pathways are known to engage in cross-talk to enhance the production of inflammatory cytokines. In the present study, we investigated the effects of gram-negative and gram-positive PGNs on bone resorption and osteoclastogenesis in the presence or absence of LPS. MATERIAL AND METHODS: We injected Escherichia coli PGN or Staphylococcus aureus PGN with or without LPS into mouse gingiva, and histopathologically assessed alveolar bone resorption by tartrate-resistant acid phosphatase staining. We also stimulated osteoclast precursors from mouse bone marrow macrophages with these PGNs in vitro and assessed osteoclastogenesis. The cells were also stimulated with synthetic ligands for NOD1; γ-D-glutamyl-meso-DAP NOD2; muramyl dipeptide or TLR2; Pam(3) CSK(4) with or without LPS to analyse the signaling cross-talk. RESULTS: S. aureus PGN, but not E. coli PGN, induced alveolar bone resorption, as did LPS. However, PGN from both sources significantly enhanced the bone resorption in the mice co-injected with LPS. Both types of PGNs induced osteoclastogenesis and accelerated osteoclastogenesis when the cells were co-stimulated with LPS in vitro. All synthetic ligands synergistically induced osteoclastogenesis by co-stimulation with LPS. CONCLUSION: Gram-positive or gram-negative PGN worked synergistically with LPS to induce bone resorption and osteoclastogenesis, possibly by co-ordinating the effects of TLR2, NOD1, NOD2 and TLR4 signaling.

Diagnostic-therapeutic algorithm for thrombotic microangiopathy. A report of two cases.

Thrombotic microangiopathies (TMA) are a group of clinical syndromes associated with haemolytic anaemia, thrombocytopenia and organ dysfunction, mainly renal or neurological. They are associated with significant morbidity and mortality, so early diagnosis and treatment are essential. In this article we report two cases of TMA; a patient with thrombotic thrombocytopenic purpura (TTP) and a patient with atypical haemolytic uraemic syndrome (aHUS).

Diagnostic-therapeutic algorithm for thrombotic microangiopathy. A report of two cases. / Algoritmo diagnóstico-terapéutico de las microangiopatías trombóticas. A propósito de 2 casos.

Thrombotic microangiopathies (TMA) are a group of clinical syndromes associated with haemolytic anaemia, thrombocytopenia and organ dysfunction, mainly renal or neurological. They are associated with significant morbidity and mortality, so early diagnosis and treatment are essential. In this article we report two cases of TMA; a patient with thrombotic thrombocytopenic purpura (TTP) and a patient with atypical haemolytic uraemic syndrome (aHUS).

Regional analgesia in postsurgical critically ill patients. / Analgesia regional en el paciente crítico posquirúrgico.

Regional analgesia intrinsically, based on its physiological effects, is routinely used for the perioperative treatment of pain associated with surgical procedures. However, in other areas such as the non-surgical treatment of acute pain for patients in a critical condition, it has not been subjected to specific prospective studies. If we confine ourselves to the physiological effects of the nerve block, in a situation of stress, the indications for regional anaesthesia in this group of patients extend to the management of a wide variety of medical as well as postsurgical conditions, of trauma patients and of other painful procedures performed in the patient's bed. The critical patient certainly must be analyzed individually as their own primary conditions is of vital importance, as well as any associated conditions they have developed that can potentially increase the risk of systemic toxicity or morbidity, such as, coagulopathies, infection, immunosuppressive states, sedation and problems associated with mechanical ventilation. This review aims to assess the role of regional analgesia in critically ill patients, placing it within the algorithm decision tree of the professional responsible for patients in critical care units, all based on the evidence of potential benefits according to the published literature.

Regulation of potassium fluxes in Saccharomyces cerevisiae.

To investigate the regulation of K+ fluxes in Saccharomyces cerevisiae the dependence of K+ efflux and Rb+ influx on [K+]i, pHi, [Na+]i, membrane potential, cell volume, and turgor pressure were studied in cells with different K+ contents. By decreasing the cell volume with osmotic shocks and the cellular pH with butyric acid the following was found. (1) The K+ efflux induced by uncouplers decreases simultaneously with the decrease of the K+ content of the cell, but the process was insensitive to [K+]i, pHi, cell volume and turgor pressure. The internal presence of Na+ inhibited this K+ efflux. (2) The increase of the Vmax of Rb+ influx observed in low-K+ cells is due to the decrease of the pHi and probably mediated by the increase of the activity of the plasma membrane ATPase. The Vmax is independent of [K+]i, [Na+]i, cell volume and turgor pressure. (3) The decrease in the Km of Bt+ influx observed in low-K+ cells does not depend directly on [K+]i, pHi, cell volume or turgor pressure. If Na+ is present, [Na+]i might be directly involved in the regulation of the Km.

[Importance of heterotrimeric G proteins in prostate cancer molecular biology]. / Importancia de las proteínas G heterotriméricas en la biología molecular del cáncer de próstata.

OBJECTIVE: To deep in the knowledge of the involvement of G-protein alphas and alphai subunits in human prostate cancer. METHODS: Prostate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein alphas and alphai subunits were studied for expression (mRNA by RT-PCR and protein by Western-blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations (analysis with restriction enzymes and cDNA sequentiation). RESULTS: At mRNA level, the expression of alphas, alphai1, alphai2 y alphai3 was detected in healthy and cancerous tissues. At protein level, the expression of alphas y alphai1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of alphai3/0 also diminished, whereas that of beta subunit was not modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the control. Digestion with restriction enzymes Eag I or AlwN I did not allow to locate mutations in alphas. However, digestion at alphai2 level with BstU I enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG). CONCLUSIONS: The functionality and expression of heterotrimeric G proteins are selectively modified in human prostate adenocarcinoma, occurring in addition some punctual mutation. The observed substitution of Gln205 by Pro may result in a low GTPase activity for alphai2 that, therefore, is stabilized in its active form.

A novel P-type ATPase from yeast involved in sodium transport.

The gene ENA1 was cloned by its ability to complement the Li+ sensitivity of a low Li(+)-efflux strain. The nucleotide sequence of the cloned DNA fragment showed that there are two almost identical genes in tandem, and predicts that they encode P-ATPases. Disruption of both genes originated a strain defective in Na+ and Li+ effluxes, and sensitive to Na+, to Li+ and to alkaline pH. By transformation with ENA1 the defective effluxes and tolerances were repaired.

Multiple sleep latency test (MSLT) and sleep apnea in aged women.

Sleep disturbance and the tendency to sleep during the day were assessed polysomnographically in 31 elderly women (mean age = 76.7 +/- 3.6 SD) recruited from a senior citizen's living facility without reference to sleep-wake complaints. The data showed that the level of sleepiness during the day in each subject depended in part on the severity of her respiratory disturbance. It was found that the group (n = 7) of elderly females with apnea and hypopnea index (AHI) higher than 20 was more sleepy [multiple sleep latency test (MSLT) = 7.9 +/- 2) than the group (n = 10) with AHI > 5 but less than 20 (MSLT = 12.7 +/- 5). Nevertheless, the presence and severity of respiratory disturbance were not the only factors that influenced the level of sleepiness during the day in the studied sample. A subgroup of four elderly females showed a marked sleepiness during the four tested periods (MSLT = 5.2 +/- 0.6) with a very low respiratory disturbance index (AHI = 5.5 +/- 0.8).

Effects of ozone exposure during pregnancy on ontogeny of sleep in rats.

Few studies regarding the effects of ozone exposure in the central nervous system (CNS), during the early stages of development have been reported. The study of sleep on newborn rats represents a model to understand the effects of this gas on the CNS. We studied the sleep organization in rats whose mothers were exposed to 1 part per million (ppm) ozone during pregnancy. We found severe sleep disturbances such as a decrease in paradoxical sleep duration and inversion of the light-dark cycle or a circadian phase-shift of vigilance states. These results suggest that ozone exposure during pregnancy may affect the generating mechanisms of paradoxical sleep, and the regulation of circadian rhythms in rats.

EEG interhemispheric correlation after callosotomy: one case study.

High interhemispheric EEG correlation (INTERr) or coherence has been interpreted as a consequence of callosal interconnections. The EEG of a callosotomized (two anterior thirds) 32-yr.-old patient was recorded during relaxed wakefulness with eyes closed. 100 2-sec. artifact-free epochs were digitally filtered into traditional broad bands and INTERr was calculated by means of Pearson product-moment coefficients. INTERr between anterior regions, where they should be expected, showed very few differences between data of this patient and those of two control groups of healthy persons. Only a few differences were observed between posterior regions where the callosum was intact. These results suggest that the role of the callosum is not crucial for INTERr and that subcortical influences and functional differentiation between hemispheres may be more plausible explanations for INTERr.

[Trichilemmal horn: a new case and review of the literature]. / Cuerno tricolémico: presentación de un nuevo caso y revisión de la literatura.

Trichilemmal horn, or trichilemmal keratosis, is an uncommon benign neoplasm of follicular lineage with trichilemmal differentiation. The essential characteristics of this tumor are its clinical presentation in the form of a cutaneous horn with trichilemmal keratinization apparent in the histology study (with a hyperplastic epithelium giving rise to dense, orthokeratotic eosinophilic keratin). We present a new case of this type of tumor in an 82-year-old woman who developed a solitary lesion on her scalp after surgical removal of a trichilemmal cyst. On the basis of the pathology report, the tumor was diagnosed as trichilemmal horn. We review the 33 reports of this tumor in the literature to date.

[Proliferative cutaneous epithelioid angiomatous nodule]. / Nódulo angiomatoso epitelioide cutáneo proliferativo.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.