A 35-Year-Old Man With Fever, Cough, and Erythematous-Erosive Mucous Membrane Lesions Accompanied by a Generalized Cutaneous Rash.

CASE PRESENTATION: A 35-year-old man presented to the ED with a 7-day history of fever, asthenia, and cough. He had previously received a 3-day course of amoxicillin and clavulanic acid (1 g tid po) and then ceftriaxone (1 g IM once per day) prescribed by his general practitioner with no substantial benefit. He was an active smoker (11.2 pack/y), without known allergy-related syndromes and any important reports in his medical history.

Experience of Uncommon EGFR Mutation in Lung Scheme Quality Program: Discussing Risks and Opportunities for the Improvement of Laboratory Response.

Background The quality programs can be considered to be a valuable tool for global and individual growth. Each result, obtained by a single laboratory, contributes to define the standardization of the response. In the case of the uncommon epidermal growth factor receptor (EGFR) mutations, the molecular result is sometimes difficult to interpret in terms of biological significance and therapy choosing. The standardization effort in the diagnostic lung setting also consists of active quality program participation. Materials and Methods The quality control analysis, which is defined as a clinical case, was performed by the extraction of DNA from FFPE sections and by RT-PCR on the EGFR (exons 19, 20, 21), BRAF, and KRAS genes. The laboratory performed a validation sequencing of EGFR exon 20 with the help of the Sanger method. Results The laboratory reported positivity for EGFR exon 20 insertions and negative results for BRAF and KRAS. The quality test finished with the redaction of a report containing the recommendation to consider the efficacy of therapy with tyrosine kinase inhibitors (TKI). This specific interpretation has determined poor performance judgment by the quality provider, which explained why most of these mutations are TKI-resistant. Conclusions This experience provides an opportunity to reflect on the critical aspects of this diagnostic setting. The detection of some uncommon EGFR mutations should entail the mutation characterization, especially for the rare exon 20 insertions, of which are not classifiable as "resistant." Moreover, this experience allows reflecting on the quality program design, mandatory actions for the laboratory, and routine activity in the oncologic multidisciplinary team.

Pleural effusion as first extra-medullary clinical presentation of an occult multiple myeloma: The role of medical thoracoscopy.

Multiple myeloma is a malignant neoplasm of plasma cells that usually invades the bone marrow replacing normal bone marrow and producing large amounts of light chains of immunoglobulins (Ig) [1]. Clinical manifestations are related to the accumulation of these proteins in vital organs such as kidney and heart. Pleural effusion may be a sign of chest involvement that occurs in approximately 6% of patients with Known multiple myeloma [2,3]. We present the case of an 80-year- old man with pleural effusion as first extra-medullary clinical presentation of an occult multiple myeloma.

Submandibular rhabdomyoma: a case report.

BACKGROUND: The cytologic diagnosis of extracardiac rhabdomyoma is frequently hampered by its rarity and resemblance to various tumors. In this regard, the infrequent occurrence has hindered its prompt and early recognition. It is also confused with other tumors because of similarities in clinical and cytologic presentations. CASE: A submandibular rhabdomyoma occurred in an otherwise-healthy, 62-year-old man. The neoplasm was firstly diagnosed by fine needle aspiration cytology (FNAC. Complete local excision without radical surgery was performed. Histologic findings confirmed the cytologic diagnosis of adult rhabdomyoma. Treatment-related complications were minimal, and there was no evidence of recurrent disease 6 years later. CONCLUSION: Helpful FNAC features and immunocytochemical results permitted an early diagnosis and spared the patient unnecessary radical surgery.

Lipid peroxidation inhibition by raxofelast improves angiogenesis and wound healing in experimental burn wounds.

We investigated the effects of raxofelast, a lipid peroxidation inhibitor, in an experimental model of burn wounds. C57BL/6 male mice of 25-30 g were immersed in 80 degrees C water for 10 seconds to achieve a partial-thickness scald burn. Animals received intraperitoneally either raxofelast (20 mg/kg/day for 14 days in 100 microL) or its vehicle alone (100 microL/day for 14 days). On day 14, burn areas were used for measuring conjugated dienes, reduced glutathione levels, histological damage, neoangiogenesis by immunohistochemistry and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, VEGF wound content, endothelial and inducible nitric oxide synthase (eNOS and iNOS) expression and wound nitrite content. Raxofelast decreased tissue conjugated dienes (vehicle 6.1 +/- 1.4 DeltaABS/mg protein; raxofelast 3.7 +/- 0.8 DeltaABS/mg protein), prevented tissue glutathione consumption (vehicle 3.2 +/- 0.9 micromol/g protein; raxofelast 6.7 +/- 1.8 mumol/g protein), increased epithelial proliferation, extracellular matrix maturation, and augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31 (vehicle 9.4 +/- 1.1 integrated intensity; raxofelast 14.8 +/- 1.8 integrated intensity). Furthermore, raxofelast enhanced VEGF wound content (vehicle 1.4 +/- 0.4 pg/mg protein; raxofelast 2.4 +/- 0.6 pg/mg protein), caused a marked expression of eNOS (vehicle 16.1 +/- 3 integrated intensity; raxofelast 26.2 +/- 4 integrated intensity) and iNOS (vehicle 9.1 +/- 1.8 integrated intensity; raxofelast 16.2 +/- 3.5 integrated intensity) and increased wound nitrite content. Lipid peroxidation inhibition by raxofelast may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

Palatine tonsils in smoker and non-smoker patients: a pilot clinicopathological and ultrastructural study.

BACKGROUND: Tobacco smoke is a well-known source of toxic, mutagenic and carcinogenic agents. The aim of the present preliminary study was to investigate the effects of cigarette smoking on lymphoid and non-lymphoid tonsillar tissue. METHODS: The study group consisted of 12 smoker and 10 non-smoker patients complaining recurrent tonsillitis. Clinical data, histological findings and scanning electron microscopic analyses were considered. To the best of our knowledge, such an approach has not been previously adopted in a similar experimental model. RESULTS: Smoker patients showed a longer history of recurrent tonsillitis, difficulties in clinical management and evident morphostructural changes than non-smokers. CONCLUSIONS: These preliminary results suggest a possible interference of cigarette smoking with the therapy response as well as a possible role of tobacco smoke in impairment of inflammatory response. Results are critically analysed and discussed. Literature data on this subject are reviewed.

Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse.

The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

Morphological changes of follicular cell basal borders and basement membranes in benign and malignant nodular lesions of the thyroid gland: an ultrastructural study.

Microfollicular nodular lesions of the thyroid gland may represent a differential diagnosis problem. Firstly, nodular areas of follicular hyperplasia have to be distinguished from follicular adenomas. On the other hand, nodular microfollicular areas exhibiting large pale nuclei, occasionally found in hyperplastic nodules and follicular adenomas, must be discriminated from latent papillary carcinomas with predominant follicular architecture. The diagnosis of follicular carcinoma still requires the detection of vascular and/or capsular microinvasion. A more refined study was planned to search for additional descriptors useful for diagnosis The authors report the results of an ultrastructural investigation carried out on 220 thyroid nodular lesions and 50 specimens of macroscopically nonnodular glands. An infolding arrangements of the thyreocyte basal border (TBB) and follicular basement membrane (FBM) was demonstrated in 50/50 nonnodular thyroid tissue specimens and 53/67 (79.1%) hyperplastic nodular lesions (p<.005). A linear arrangement of the TBB and FBM was found in 85/121 (70.2%) follicular adenomas and in 32/32 differentiated carcinomas (p<.001). In the last group, 12/32 (37.5%) cases showed focal discontinuities of FBM. In conclusion, the benign thyroid nodules show a prevalently infolding arrangements of TBBs, whereas the majority of proliferative lesions display a linear morphology. In absence of an infiltrating pattern there is no morphological evidence of discriminating potentially malignant vs. benign lesions. The linear distribution of TBBs and FBMs places the case in a group of borderline lesions that involve a more careful postsurgery investigation.

Wegener's granulomatosis presenting with otologic and neurologic symptoms: clinical and pathological correlations.

A case of Wegener's granulomatosis in a 59-year-old woman is reported. The disease first involved the parotid gland, the brain stem and the spinal cord, then running a rapidly progressive course as systemic pathology. Anti-neutrophil cytoplasmic antibody (cANCA) levels raised as renal failure set in. Renal biopsy confirmed the diagnosis of Wegener's granulomatosis and an appropriate therapy was adopted.

Effect of recombinant adeno-associated virus vector-mediated vascular endothelial growth factor gene transfer on wound healing after burn injury.

OBJECTIVE: The purpose of this study was to investigate the effect of recombinant adeno-associated viral (rAAV) vector-mediated human vascular endothelial growth factor (VEGF165) transfer on experimental burn wounds. DESIGN: Randomized experiment. SETTING: Research laboratory. SUBJECTS: C57BL/6 male mice weighing 25-30 g. INTERVENTIONS: Mice were immersed in 80 degrees C water for 10 secs to achieve a partial-thickness scald burn. Animals were randomized to receive at two injection sites on the edge of the burn either 1011 copies of the rAAV-VEGF165 or the vector carrying the control and inert gene beta-galactosidase (rAAV-LacZ). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of VEGF expression (immunohistochemistry) and VEGF wound content (enzyme-linked immunosorbent assay), determination of wound nitrite, and measurement of messenger RNA (mRNA) for endothelial and inducible nitric oxide synthase (eNOS and iNOS). MEASUREMENTS AND MAIN RESULTS: rAAV-VEGF165 increased epithelial proliferation, angiogenesis, and maturation of the extracellular matrix. Furthermore, gene transfer enhanced VEGF expression, studied by immunohistochemistry, and the wound content of the mature protein (rAAV-LacZ, 11 +/- 5 pg/wound; rAAV-VEGF165, 104 +/- 7 pg/wound). Moreover, VEGF165 gene transfer increased wound content of nitrate. Finally, rAAV-VEGF165 administration enhanced the messenger RNA for eNOS (rAAV-VEGF165, 1.1 +/- 0.2 relative amount of eNOS mRNA; rAAV-LacZ, 0.66 +/- 0.3 relative amount of eNOS mRNA) and iNOS (rAAV-VEGF165, 0.8 +/- 0.09 relative amount of iNOS mRNA; rAAV-LacZ, 0.45 +/- 0.05 relative amount of iNOS mRNA). CONCLUSION: Our study suggests that rAAV-VEGF gene transfer may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps.

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.