Comparison of Sodium Selenite and Selenium-Enriched Spirulina Supplementation Effects After Selenium Deficiency on Growth, Tissue Selenium Concentrations, Antioxidant Activities, and Selenoprotein Expression in Rats.

Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 µg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 µg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus.

Prognostic value of tyrosinase reverse transcriptase PCR analysis in melanoma sentinel lymph nodes: long-term follow-up analysis.

OBJECTIVE: To determine the prognostic value of detecting tyrosinase transcripts in melanoma sentinel lymph nodes (SLNs). METHODS: Reverse transcription (RT) PCR for tyrosinase mRNA was performed on negative SLNs of 76 patients with melanoma. RESULTS: Tyrosinase mRNA was found in 39 patients (51.3%). After a median follow-up period of 51 months, significant differences were found in overall survival (OS) but not in disease-free survival (DFS). The 5-year OS and DFS rates were 97.2% and 80%, respectively, for RT-PCR tyrosinase-negative (TN) patients vs. 78.67% and 66.24% for RT-PCR tyrosinase-positive (TP) patients (P = 0.019 and P = 0.38, respectively). Of four progressing patients in the TN group, three relapsed with subcutaneous, soft-tissue or lymph-node metastases, while seven out of nine progressing patients in the TP group relapsed at visceral sites. CONCLUSIONS: No significant differences in DFS were found by RT-PCR tyrosinase expression analysis at melanoma SLNs. Significant differences in OS could be related to a different pattern of relapse and must be confirmed after a longer follow-up time.

Atypical schwannoma of the median nerve. A case report.

Schwannomas of the hand are very rare tumors and represent less than 3% of all soft tissue tumors in the hand. These tumors share clinical, epidemiological and imaging characteristics with the other soft tissue and peripheral nerve tumors; thus, it can be difficult to make a preoperative diagnosis. Here we report the case of a 48-year-old woman who presented with a schwannoma arising from the palmar branch of the median nerve. The tumor measured 54 × 41 x 52 mm and was located in the thenar eminence. The first hypothesis was a vascular tumor. After surgery and histological analysis, the final diagnosis of an atypical schwannoma was established. The presence of shared immunohistochemical characteristics with cellular histiocytoma and myoepithelial tumors forced us to adopt an aggressive follow-up protocol. As of the last follow-up at 9 years, the patient had good clinical outcomes and no recurrence. This case highlights the difficulties encountered in clinical practice to diagnose such tumors.

Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma.

BACKGROUND: Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. PATIENTS AND METHODS: Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. RESULTS: High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). CONCLUSION: Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.

[Incidence of distal ulna fractures associated with distal radius fractures: Treatment options]. / Incidence des fractures de l'extrémité distale de l'ulna associées aux fractures de l'extrémité distale du radius (processus styloïde ulnaire). Nos choix thérapeutiques.

Fractures of the neck and/or head of the ulna or distal ulna fracture (DUF) other than ulnar styloid fractures can occur in combination with distal radius fractures (DRF). This combination can have a significant influence on the treatment and prognosis since it causes the entire distal forearm to be unstable. In a series of 1279 consecutive unilateral DRFs, we found an associated ulnar neck fracture in 5.9% of cases, ulnar head and neck fracture in 1.6%, and isolated ulnar head fracture in 1.4%. Overall, 9% of cases in this study had a DUF with a DRF. The frequency of extra-articular "A" (11%) and intra-articular "C" (9%) DRFs according to the AO classification was about the same. There were no cases of DUF combined with partial "B" DRF. There was a correlation between combined DUF with DRF and the patient's group in the PAF classification. DUF are more frequently associated with DRF in elderly patients. Specific distal ulnar locking plates were recently introduced and they may be a useful adjunct to distal radius locking plates when treating patients with combined DUF and DRF.

Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis.

PURPOSE: Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS: A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS: Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P < .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION: The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.

S-100beta and MIA in advanced melanoma in relation to prognostic factors.

We compared the sensitivity and specificity of S-100 and MIA in advanced melanoma, in 96 patients with no evidence of disease (NED) and 86 patients with metastatic melanoma. Abnormal S100 (>0.2 microg/l) and MIA (>14 ng/ml) results were found in 1.1% and 3.2% of NED patients and in 59.3% and 54.6% of the patients with active melanoma (p<0.001). Using both tumor markers simultaneously, the sensitivity increased up to 69.8% with the same specificity 96.8%. S100 serum levels were not related to growth patterns. By contrast, MIA levels seemed to be related to the growth pattern, with higher levels in nodular melanoma (60.6+/-87.1 ng/ml) compared with acral-lentigous melanoma (11.9+/-5.4 ng/ml) (p=0.02). Likewise, S100 was related to the metastases site with significantly higher sensitivity and mean concentrations in patients with brain metastases (p=0.01) with the lowest in those with lung MI. MIA was related to the same metastases locations but without statistical significance. In summary, both S100 and ML4 are useful markers related to prognostic factors, being more effective when used in combination.

Prognostic significance of the detection of circulating malignant cells by reverse transcriptase-polymerase chain reaction in long-term clinically disease-free melanoma patients.

The purpose of this study was to assess the prognostic significance of the detection of circulating melanoma cells by reverse transcriptase-PCR in long-term clinically disease-free melanoma patients. Patients with melanoma who were free of clinical relapse for at least 6 months after primary tumor diagnosis were included and prospectively followed. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase-PCR at the time of their inclusion in the study. One hundred six blood samples from 57 melanoma patients were analyzed. The median time between melanoma diagnosis and inclusion in the study was 24 months (range, 7-51 months). The median follow-up time calculated from the time of inclusion in the study was 27 months (range, 11-36 months). Tyrosinase mRNA in blood was detected in 10 (17.5%) of 57 patients: 2 (18%) of 11 stage I patients, 6 (19%) of 33 stage II patients, and 2 (15%) of 13 stage III patients. Actuarial 2-year DFS was 89% for the tyrosinase-negative patients versus 30% for the positive patients (P = 0.003). Actuarial 2-year OS was 97% for the tyrosinase-negative patients versus 72% for the positive patients (P = 0.001). Tyrosinase mRNA could be detected in the blood of a proportion of long-term disease-free melanoma patients, regardless of their initial clinical stage. The presence of late circulating melanoma cells in this selected group of clinically disease-free patients was significantly associated with a subsequent high risk of relapse and death.

Large deletions of chromosome 9p in cutaneous malignant melanoma identify patients with a high risk of developing metastases. Hospital Clinic Malignant Melanoma Group, University of Barcelona.

Cutaneous malignant melanoma (CMM) is an aggressive tumour with a high metastatic potential. Deletions of chromosome 9p have been detected in CMM, some of which involve the CDKN2A/p14ARF genes. Loss of heterozygosity (LOH) of 16 microsatellite markers on 9p and mutations in the CDKN2A/p14ARF genes had been previously studied in 32 melanoma patients by our group. 9p deletions were detected in 15 primary tumours (45.5%) and are here correlated with the clinical outcome over 5 years and compared with classical prognostic factors. Eight of the 32 patients developed metastases (25%). The metastases were all detected within 768 days of the initial diagnosis. The patients without metastases were last monitored at least 1621 days after diagnosis. None of the 21 patients with more than eight microsatellites conserved developed metastases, whereas all of the eight patients who developed metastases had eight or more markers deleted. The sensitivity of this analysis to predict metastases was 100% (specificity 84%), whereas the sensitivity for the same sample using a Breslow thickness > 3 mm was 62.5% (specificity 68%). LOH of eight or more of the 9p microsatellite markers is therefore a useful prognostic factor to predict the development of metastases in the first 4.4-6.3 years (1621-2294 days).

The use erythrocyte glutathione as a predictive marker for malignant melanoma.

BACKGROUND: Glutathione (GSH) may provide defense against reactive oxygen species (ROS) generated by ultraviolet radiation. Furthermore, some authors have demonstrated a relationship between the GSH of peripheral blood erythrocytes (GSHe) and resistance to chemotherapy. PATIENTS & METHODS: To observe the influence of GSH on the genesis and evolution of Malignant Melanoma (MM), we assessed the concentration of GSH in erythrocytes (GSHe) in MM patients (n = 566) and controls (n = 164) by the method of Beutler (1963). RESULTS: No differences were found between the two groups (5.94 +/- 1.61 cases vs 6.08 +/- 1.49 mmol/gr Hb, controls; p > 0.05). Fifty seven patients with poor evolution (disease-free survival < 2 years) had higher GSH levels than the remaining patients (6.35 +/- 1.83 vs 5.83 +/- 1.62 mmol/g Hb; p < 0.01). GSHe increased significantly after antineoplastic therapy (4.75 +/- 1.26 vs 7.73 +/- 1.39 mmoVg Hb; p < 0.001), thus indicating a possible role in chemoresistance. 2 CONCLUSIONS: GSHe is not related to the risk of developing MM. GSHe may be related to the evolution of MM, being higher in patients who suffer relapse or metastasis. GSHe increases significantly during cytostatic treatment.

Mid-arm sentinel lymph nodes showing surprising drainage from a malignant melanoma in the forearm.

A 51-year-old man with a malignant melanoma in his left forearm was studied to detect the sentinel lymph node and to assess the possibility of micrometastases in regional lymph nodes. Lymphoscintigraphy demonstrated two sentinel lymph nodes in the midarm. Two other nodes in the same location as well as in the left axilla were also observed. The exact location of the sentinel lymph nodes was identified with a gamma-ray detector. At the time of surgery, blue dye was injected around the primary lesion and the two sentinel lymph nodes on the inner side of the left arm were resected. Both lymph nodes were pigmented black. The histopathologic study demonstrated metastases from malignant melanoma in both nodes. This case reflects the main role of lymphoscintigraphy in identifying draining lymph nodes in unusual locations as observed in this patient.

[Sentinel lymph node detection with lymphoscintigraphy and intraoperative probe in malignant melanoma patients]. / Detección del ganglio centinela mediante linfogammagrafía y sonda detectora intraoperatoria en pacientes con melanoma maligno.

BACKGROUND: The sentinel lymph node is the first node in a lymphatic basin to receive lymphatic drainage from a tumor site. If this node is free of tumor, then radical lymphadenectomy may be avoided. The goal of this study was to assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the sentinel node detection in patients with malignant melanoma. METHOD: We prospectively studied 40 patients with malignant melanoma (24 in I/II stages and 16 in III stage). The day before surgery a lymphoscintigraphy with 99mTc-nanocolloid was performed and the first lymph node identified was considered as sentinel node. For intra-operative mapping a hand-held gamma probe was used. RESULTS: Sentinel nodes were identified in 39/40 (97.5%) patients. In 24 patients with I/II stages 34 sentinel nodes were demonstrated (six positive and 28 negative for malignant melanoma). A total amount of 161 regional lymph nodes was harvested, all of them being negative for malignant melanoma. In 16 patients with III stage, 22 sentinel nodes were located (14 positive and eight negative for malignant melanoma). A total of 89 regional lymph nodes were excised in sentinel nodes positive patients (44 positive and 45 negative for malignant melanoma) and 36 lymph nodes in sentinel node negative, all of them negative for malignant melanoma. CONCLUSIONS: In patients with malignant melanoma, lymphoscintigraphy with 99Tc-nanocolloid is useful for the detection of sentinel lymph node. Biopsy of this node is useful for the selection of patients to undertake a lymphadenectomy.

[Cerebral metastasis of melanoma: study of 48 patients]. / Metástasis cerebrales de melanoma: estudio de 48 pacientes.

BACKGROUND: Malignant melanoma is a frequent cause of cerebral metastases (CM). In the present study the characteristics of primitive melanomas of patients with CM, their forms of clinical presentation and treatment were analyzed. METHODS: A retrospective study of the patients with melanoma and CM diagnosed between 1982 and 1991 was carried out. RESULTS: Out of 786 patients with melanoma 48 were identified with CM. In 65% of the melanoma originated in cutaneous areas BANS (of bad prognosis). The median thickness of the tumor (Breslow's index) was of 3.6 mm. The median period of latency between diagnosis of the melanoma and the detection of CM was 22 months. Although recent hemorrhage of the CM was observed in the cranial computerized tomography in 20 of the 48 patients, only 7 presented clinical symptoms of ictus. In 23 patients the CM were the only evidence of metastases of the melanoma. The median survival was one month in the patients treated with only dexamethasone, 3.5 months in the chemotherapy group, 2.5 months for the group given radiotherapy and 6 months for those undergoing surgery. CONCLUSIONS: Most of the patients with cerebral metastasis had a primitive melanoma with criteria of bad prognosis. The presence of hemorrhage in computerized tomography did not always correlate with clinical symptoms of ictus. Surgical treatment must be considered in patient with sole cerebral metastasis without evidence of distant disease.

[Primary malignant melanoma of the skin. Retrospective study of 375 cases. Clinical aspects and histology]. / Melanoma maligno cutáneo primitivo. Estudio retrospectivo de 375 casos. Clínica e histología.

The clinical and histologic features of 375 cases of primary malignant melanomas of the skin diagnosed and/or treated in the Hospital Clinic i Provincial (Barcelona, Spain) over a seven years period (1981-1987) were evaluated. The analysis of data showed many differences between these cases and those previously reported by us or from other countries. Sex incidence showed an increased frequency in women (58%), and a high incidence on lower limb in female (26% of all cases). Superficially spreading melanoma was the most common type (58%), followed by nodular melanoma (27%), acral lentiginous melanoma (8%) and lentigo maligna melanoma (6%). 57% of cases were diagnosed when the tumor thickness indicated a moderate or high-risk.

[Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. An analysis of 67 cases with a study of the prognostic factors]. / Sarcoma de Kaposi asociado a síndrome de inmunodeficiencia adquirida. Análisis de 67 casos con estudio de factores pronósticos.

The features and prognostic factors of 67 cases of Kaposi's sarcoma (KS) associated to the acquired immunodeficiency syndrome (AIDS) diagnosed at the Hospital Clinic, Barcelona, are analyzed. All the patients were male; mean age was 39.7 years, ranging from 22 and 62 years. 64 were homosexuals (95.5%), two were homosexual-drug addicts (3%) and one was drug addict (1.5%). Prevalence of cytomegalovirus and herpes virus infections were 91.1% and 89.5% respectively. In 42 cases (62.7%) KS was the initial AIDS presentation. The most common localization was the skin (89.5%), followed by the digestive tract (52.2%) and the lymph nodes (22.4%). Staging distribution was: 20 patients (29.8%) were in stage I, 11 patients (16.4%) in stage II, 7 patients (10.4%) in stage III, and 29 patients (43.2%) in stage IV. Constitutional symptoms associated to KS were found in 37 patients (55%). Overall 39 patients have already died, and the actuarial survival possibility of these 67 cases was 55% after 12 months. Univariant statistical analysis showed the presence of six variables with prognostic significance (p less than 0.05): staging, symptomatology, total white blood count, total lymphocyte count, T helper lymphocyte count and hemoglobin. Multivariant statistical analysis only chose the staging and symptomatology variables as independent (p less than 0.01 and p less than 0.001, respectively).

[Detection of sentinel lymph nodes by lymphatic gammagraphy and intraoperative gamma-ray probe in patients with malignant melanoma. Initial results]. / Detección del ganglio centinela mediante linfogammagrafía y sonda de rayos gamma intraoperatoria en pacientes con melanoma maligno. Primeros resultados.

In the last years there has been an arising concern in the sentinel lymph node identification, the first lymph node to receive direct draining from the primary tumour, specially in malignant melanoma (MM). We studied 20 patients with MM: 10 with palpable regional lymph nodes and 10 without palpable LN by performing a lymphoscintigraphy using 99mTc-nanocolloid and a gamma-ray detecting probe during the surgery to locate the sentinel lymph node. In patients with palpable LN, 13 sentinel lymph nodes were identified. Ten of them were MM involved. Furthermore, 82 LN were harvested from involved lymph basins and 30 of them were positive for MM. In patients without palpable LN, 14 sentinel lymph nodes were identified (3 positives and 11 negatives for MM) and other 76 LN were resected (all of them negative). There were not <> in any patient. These preliminary results support the utility of the technique for the diagnosis and lymphadenectomy selection in patients without palpable LN but which could be involved by micrometastases.

[Focal epidermal necrolisis. A variation of lupus erythematosus of a new disease?]. / Necrolisis epidérmica focal una variedad de lupus eritematosos o una nueva enfermedad?

Four cases with clinical characteristics closely related to Lupus Erythematosus Disseminatum are reported by the authors. The evolution, progress and the biochemical, immunological and photobiological data were different from those usually found in L.E.D. The histopathological picture was also dissimilar, the most characteristic finding being a sharply limited epidermal necrolysis with focal distribution. In view of the peculiarities of the clinico-pathological syndrome presented by these patients, the authors raise the questions does it represent a special modality of L.E.D. or a new lupus-like disease?

[Contact dermatitis caused by ethylene oxide]. / Dermatitis de contracto por óxido de etileno.

A case of contract sensitization to the ethylene oxide by a mask sterilized with this substance is reported. The mask was correctly sterilized but the ethylene oxide was not completely evaporised. The path tests were positive in the patient but negative in 25 control subjects. The patch tests with the international series and with all the elements of the mask were negative. The possible troubles of ethylene oxide and the sterylisation methodes of this substance are reviewed.

[Unusual side effects in patients with psoriatic erythroderma treated with etretinate (RO 10-9359)]. / Efectos secundarios inhabituales en enfermos con eritrodermia psoriásica tratados con etretinato (RO 10-9359).

The results of the treatment of psoriatic erythroderma are variable in different references. The authors describe the treatment of three patients and emphasize the immuno-modulatory action of etretinate on polymorphonuclears, monocytes and Langerhans cells and the possibility of an action on prostaglandins.

[Toxic skin reaction caused by hydantoins in a patient with AIDS]. / Toxicodermia por hidantoínas en paciente con SIDA.

A case of clinically characteristic hypersensitivity reaction to phenytoin in a AIDS patient with cerebral toxoplasmosis is reported. There was response to therapy with systemic steroids. Laboratory data and histopathologic features of the skin are reported.