Medicamentous thrombolysis disguises pulmonary thromboembolism as a cause of death.

We report the case of a 31-year-old female who was admitted to the emergency department with symptoms of cardiac arrest and ultimately died in spite of enormous resuscitation efforts. During resuscitation, pulmonary embolism was considered as a possible non-cardiac cause of cardiac arrest, and following its extremely unfavorable prognosis, the fatal outcome was not so surprising. However, since acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments was suspected, alteplase was indicated and administered. At the autopsy, no venous thrombosis in the vena cava, pelvic veins, or any of the lower extremity veins was documented; conversely, nor were specific signs of pulmonary thromboembolism (PTE) found macroscopically, until this was confirmed by histopathological staining which is not used as a routine diagnostic tool in forensic medicine. In this study, we conclude that PTE is generally overlooked as the principal diagnosis and the cause of death. Rightful postmortem diagnosis could lead to increased vigilance and a change in management in many of such cases, which could result in improved survival. Motivated by providing better awareness of PTE, this study aimed to illustrate unrecognized PTE and pathological findings that were masked by thrombolytic drugs.

Modulating telomerase activity in tumor patients by targeting dyskerin binding site for hTR.

Telomeres shortening, which leads to apoptosis, is prevented by telomerase adding small repeated segments of DNA to the telomeres. The telomerase level has been correlated with progression of several cancer types, including acute leukemia, breast, prostate, lung cancer and melanoma. Suppression of telomerase activity was found to reduce metastatic potential but could have serious side effects in normal proliferative cells. One of the proteins stabilizing the telomerase complex called dyskerin reduces the maximum telomerase activity. We suggest a possible therapeutic agent which would disable the interaction of dyskerin and telomerase, but would not completely inhibit telomerase activity.

Detection of melanoma cells in sentinel lymph nodes by reverse transcriptase-polymerase chain reaction: prognostic significance.

BACKGROUND: Recently reverse transcriptase-polymerase chain reaction (RT-PCR) has been proposed as a new sensitive method for the detection of submicroscopic melanoma nodal metastases. Sentinel lymph node (SLN) status is considered the most important prognostic factor for melanoma patients. Thus, in recent years, melanoma research has been focused on identifying new molecular markers of micrometastases. METHODS: In this study, 129 SLNs were collected and analyzed by RT-PCR for tyrosinase and melanoma inhibitory activity (MIA) messenger RNA (mRNA) expression. RESULTS from PCR analysis were then compared with those obtained by hematoxylin and eosin and immunohistochemistry and related to progression of disease. RESULTS: MIA gene expression was positive by RT-PCR in 27% of the tyrosinase-positive SLNs. When the correlation between tyrosinase and/or MIA mRNA expression and disease-free survival was evaluated by the Kaplan-Meier exact test, there was a statistically significant correlation between simultaneous tyrosinase and MIA gene expression in SLNs and progression of disease. CONCLUSIONS: RT-PCR analysis for both MIA and tyrosinase mRNA may identify a subset of melanoma patients with a worse prognosis whom the routine methods, such as histology and immunohistochemistry, fail to identify because of the poor sensitivity of these methods.

Perforin expression is upregulated in the epidermis of psoriatic lesions.

BACKGROUND: There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. OBJECTIVES: To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. METHODS: Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. RESULTS: We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. CONCLUSIONS: Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque.

Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planus.

BACKGROUND: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. OBJECTIVES: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes (PBL) in exacerbation and remission phases of the disease as well as in skin lesions. METHODS: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. RESULTS: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+ perforin+ cells) in the exacerbation phase of disease (P < 0.05), which was mostly located in the CD8+ subpopulation (CD8+ perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+ and CD8+ phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). CONCLUSIONS: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.

Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanoma.

Depth of invasion and stage of the disease are well known prognostic indicators in cutaneous melanoma (CM). However, the role of other parameters, such as the variations in cytomorphology of melanocyte tumours, mitotic activity and angiogenesis is still open to question. The aim of this study was to analyse proliferation by mitotic activity index (MAI) and immunostaining of proliferating cell nuclear antigen (PCNA), and the intensity of neovascularization (microvessel density; MVD) in CM clinical stage I in relation to epithelioid, spindle and nevoid cell type, histological type (superficial spreading melanoma and nodular melanoma), Clark's level and Breslow thickness. Finally, the role of all parameters in the prognosis of CM was evaluated. Statistical analysis demonstrated that cytological characteristics of CM correlate only with Clark's level, while histological types correlate with MAI, PCNA and MVD. MAI and PCNA also showed correlation between groups according to Clark's level and Breslow thickness. Finally, tumour cell PCNA was found to correlate with MVD. Survival of patients with CM correlated significantly with MAI. These results suggest that cytological variation, histological type, PCNA and MVD alone are not independent prognostic parameters, whereas MAI is a potentially important prognostic marker in CM.

Influence of tumor thickness and vascularity on survival in cutaneous melanoma.

Eighty-eight cases of cutaneous melanoma (CM) were analyzed in order to elucidate the relationship between thickness, angiogenesis, and prognosis. The thickness of the tumor was measured according to the Breslow method, and the microvessels were identified by an immunohistochemical study using anti-factor VIII monoclonal antibody on specimens from 40 patients with superficial spreading melanoma (SSM), and 48 with nodular type (NM). Microvessels were counted in the area of highest density. The overall survival and disease-free period were analyzed retrospectively. The proportion of patients with thicker CMs (> 1.5 mm) increased with age in both sexes. Mean vascular count was statistically significant different only between thinner and thicker tumors in the SSM group (P < 0.05). Prognosis was correlated with the thickness of CM (P = 0.0002), mean vascular count alone (P = 0.004), mean vascular count in association with CM thickness less than 1.5 mm (P = 0.0005), and with mean vascular count in NM (P = 0.02). These findings suggest that increasing microvessel density indicates a worsening prognosis.

Severe Trichinellosis cured with pulse doses of glucocorticoids.

Trichinellosis is a worldwide zoonotic disease caused by a nematode Trichinella spiralis. We studied a case of Trichinella spiralis infection with severe eye involvement, febrile condition, generalised malaise and muscular weakness in a young female patient. Comprehensive ophthalmologic, infectologic, neurological and immunologic examinations including electro diagnostic tests and CT scan of the head were performed, but the diagnosis was confirmed only by histological examination of biopsy specimens of skeletal muscle. The patient did not respond to standard corticosteroid therapy and improved only after pulse doses of 1000 mg methylprednisolone. Although most authors recommend moderately high doses of corticosteroids in the treatment of Trichinellosis, in severe cases extremely high doses might be necessary.

Lethal midline granuloma starting as granuloma laryngis.

We report a case of lethal midline granuloma in a 34-year-old male patient. The patient was referred to our hospital because of long-lasting hoarseness. He was treated for granuloma laryngis. After two years nasal obstruction developed followed by ulceration of the hard palate and destruction of part of the nose and the upper lip. A biopsy demonstrated polymorphic infiltrate consisting of small lymphocytes, plasma cells, macrophages, atypical lymphoid cells and eosinophils. Radiotherapy was very effective and led to long-term remission. The different etiological aspects of this syndrome are discussed.

A 20-year epidemiological study of cutaneous melanoma in the Rijeka district of Croatia.

A retrospective study was made of the incidence of cutaneous melanoma among the population of the district of Rijeka (Croatia) during the period 1977-96. A total of 397 patients with cutaneous melanoma was documented during this period. Over the 20-year period the incidence of the tumour increased, the mean annual rate being 4. 8 (4.0 in males and 5.4 in females) in the first 10-year period and 7.16 in the second (7.1 in males and 7.3 in females). The number of registered cases in males and females was almost identical (1 : 1.05). The number of melanoma cases increased with age in both sexes, whereas it was rare in children. The most affected anatomical location was the trunk in males and the lower limbs in females. The results indicate the need for active prevention and educational programmes in this population.

CD30-positive cutaneous anaplastic large cell lymphoma with ichthyosis acquisita.

Anaplastic large cell lymphoma (ALCL) is a high-grade non-Hodgkin's lymphoma recognized by the expression of the CD30 marker and by its morphology. We report an unusual case of ALCL in a 42-year-old woman. For ten years the patient only had pruritic erythematous skin lesions, then a plaque with nodules and ulcers on the right thigh and leg developed, followed by ichthyosis acquisita. The development of ALCL in women and the association of ichthyosis acquisita with this type of lymphoma are uncommon.

Azithromycin compared with minocycline in the treatment of acne comedonica and papulo-pustulosa.

This open study was conducted in 72 outpatients with acne vulgaris, to compare the clinical efficacy and tolerability of azithromycin and minocycline. Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles every 10 days and minocycline was administered 100 mg daily for 6 weeks. Improvement was assessed 6 weeks after initiation of treatment with a four-graded scale. A satisfactory clinical response was observed in 75.8% of the patients treated with azithromycin and in 70.5% of those treated with minocycline. There were no significant differences between these two acne treatments in terms of reduction of the number of lesions (p> 0.05). Both agents were well tolerated and mild side effects were reported in 10.3% of azithromycin and 11.7% of minocycline treated patients. We conclude that azithromycin is at least as clinically effective and well tolerated as minocycline as treatment of facial comedonic and papulopustular acne.

Nuclear grade in invasive ductal breast carcinoma. Comparative study on nuclear grade and morphometric parameters, hormonal receptor status, flow cytometric analysis and lectin histochemistry.

Histologic and nuclear grading (NG) have been widely used to predict the prognosis in patients with advanced breast cancer. However, NG has been criticized as a non-standard (several grading schemes used) and subjective (significant interobserver variability) method for predicting the biologic behavior of this tumor. Our results on 106 invasive ductal breast carcinomas demonstrate that NG correlates with morphometric prognostic index (MPI) (p < 0.007) (lower value of MPI is connected with lower NG of 1-2 and better prognosis), with estrogen receptor (p < 0.0002) and progesteron receptor status (p < 0.04) (hormonal receptor positive tumors having lower NG). NG correlates with s-phase fraction (SPF), p < 0.04, values lower than 9.6% corresponding to lower NG. We consider NG to give important information about the biologic behavior of the tumors under observation, demonstrating a good correlation with more established parameters such as MPI and SPF.