Nucleolin protein expression in cutaneous melanocytic lesions

Background:  Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.
Methods:  We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results:  Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion:  An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma.     

Is the evidence from clinical trials for cardiovascular risk or harm for glitazones convincing?

Thiazolidinediones (TZDs), agonists of the nuclear receptor peroxisome proliferator-activated receptor-γ, induce the expression of many genes, including several enzymes and transporters involved in glucose and lipid metabolism. Although the efficacy of TZDs on blood glucose control in type 2 diabetes is not questionable, their cardiovascular effects have been debated, with beneficial or harmful actions suggested by different authors. This article reviews the available clinical evidence on the cardiovascular effects of TZDs, discussing possible mechanisms underlying the observed effects and suggesting some directions for future research.     

Hemophilia: State of the Art of Hematologic Care 1988

Since 1982, when the World Federation of Hemophilia first published a document on the state of the art of hemophilia diagnosis and care, there have been lights and shadows in this field. Although the widespread infection of hemophiliacs with the human immunodeficiency virus (HIV) contaminating clotting factor concentrates is still a threatening and formidable shadow, the gloomy picture brought about by the AIDS epidemic is partially lightened by spectacular improvements in therapy and diagnosis. Carrier detection and first-trimester prenatal diagnosis can now be performed accurately in most kindreds by analysis of DNA of the factor VIII or IX genes. An important step forward towards the elimination of the risk of blood-borne infections transmitted by plasma products was recently made through the application of virucidal methods to clotting factor concentrates. Since HIV appears more vulnerable to such methods than the hepatitis viruses, currently available concentrates can be considered substantially free from the risk of transmitting HIV infection. Even though transmission of hepatitis is much reduced but not totally abolished, virucidal methods are continuously being improved, so that it can be foreseen that concentrates will become safer and safer. Finally, factor VIII produced by recombinant DNA technology is undergoing the first clinical trials in hemophiliacs. Hopefully, it will free from the risk of transmitting infections and will be available in sufficiently large amounts to meet the need of hemophiliacs worldwide. In 1982, the World Federation of Hemophilia published a message on the status of diagnosis and treatment of hemophilia. Since then, hemophilia care has been complicated by widespread infection of hemophiliacs with human immunodeficiency virus (HIV).(ABSTRACT TRUNCATED AT 250 WORDS)     

Arthroscopic Latissimus Dorsi Transfer

The patient is placed in lateral decubitus. A 6-cm incision made in the axilla allows access to the latissimus dorsi tendon and its neurovascular pedicle. Holding the arm in internal rotation, the surgeon detaches sharply the tendon off the humeral shaft and then reinforces it with wrapping sutures. Pulling the free limbs of the sutures exposes the under surface of the muscle and helps to identify the neurovascular pedicle. Special lighting retractors suited for a large diameter scope are helpful. Mobilization is completed when 2 cm of the tendon crosses the posterior edge of the acromion. The standard lateral portal is used for visualization. A silicon drain tube stiffened by a Wissinger rod is advanced from the posterior portal under direct visualization in the space between teres minor and deltoid, exiting in the auxiliary incision. A suture loop passed down the tube retrieves the tendon sutures out the posterior portal. These are then moved out the anterior portal, thus pulling the tendon over the tuberosity. The first anchor is inserted at the anterior aspect of the greater tuberosity, close to the articular cartilage and long head of the biceps tendon. Two to 3 anchors are inserted fixing the tendon to the tuberosity until it is stable.     

Progression to AIDS among Italian HIV-seropositive haemophiliacs. Italian Group

To investigate the interval between HIV-1 infection and the development of clinical AIDS among Italian patients with congenital coagulation disorders, a national cohort study was undertaken in 1988. Information was collected both retrospectively and prospectively on 499 HIV-1-positive patients enrolled in an ongoing national registry of patients with congenital coagulation disorders. Two methods were used to estimate each patient's seroconversion date: the mid-point between the last negative (either known or estimated) and the first positive test, and the median under a Weibull distribution, which was assumed to fit seroconversion data. The two methods of estimating the seroconversion time yielded similar results. The actuarial incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 12.8% (95% confidence interval = 9.7-15.9) over 7 years for Italian haemophiliacs. Progression appears to be slow in the first 5 years after the infection, and to rise steadily thereafter. A strong association between faster progression and older age at seroconversion was found. Zidovudine-treated individuals seem to have a slower progression than untreated individuals, after controlling for CD4, but there was no association between progression and type and severity of the congenital disorder.     

Giant cavernous hemangiomas: Diagnosis and surgical strategies

From January, 1972 to June, 1989, 51 patients with liver hemangiomas (32 females and 19 males, mean age 35 years) were evaluated for surgical treatment. Diameters of the masses were 5 cm to 20 cm (median 8.5 cm). Nine of the patients had already been treated for cancer. Twenty-two (43.1%) of the 51 patients were symptomatic and 29 (56.9%) patients were asymptomatic. In 34 patients (66.7%) a definite diagnosis of hemangioma was made by scintiscan and/or ultrasound and/or computed tomography and/or angiography while in the remaining 17 (33.3%) patients the diagnosis was uncertain. The most common indications for resection were the presence of a symptomatic angioma, a symptomatic mass with an uncertain diagnosis, and/or lack of a definite pre-operative diagnosis. Surgery was performed on 25 patients. Ten anatomic and 15 atypical resections or enucleations were performed. There were no postoperative deaths. Two further patients, operated for probable hemangioma, were found to have primary hepatic malignancies. In the 26 unresected patients, no complications were observed during follow-up. In 3 patients, hemangioma enlargement was detected by ultrasound, but there were no symptoms. As cavernous liver hemangiomas are now more reliably diagnosed and their natural history is usually uneventful, surgery can be avoided in most cases. However, when a non-resection policy is adopted, an exact diagnosis is essential in order to rule out primary or metastatic cancer. Surgical exploration and treatment should be limited to symptomatic or complicated cases as well as to patients with an uncertain diagnosis.

---

Resumen Cincuenta y un pacientes con hemangiomas del higado (32 mujeres y 19 hombres, edad promedio 35 años) fueron valorados en cuanto a tratamiento quirúrgico en el período enero 1972 a junio de 1989; el diámetro de las lesiones oscilo entre 5 y 20 cm (promedio 8.5 cm). Nueve de los pacientes ya habían sido tratados por cáncer; 22/51 (43.1%) estaban sintomáticos y 29/51 (56.9%) eran asintomáticos. En 34/51 (66.7%) se hizo el diagnóstico definitivo de hemangioma mediante escintigrafia y/o ultrasonido y/o tomografía computadorizada y/o angiografia, en tanto que en los otros 17 pacientes (33.3%) el diagnóstico resultó incierto. Las indicaciones más comunes para resección fueron: presencia de un angioma sintomático, una masa asintomática con diagnóstico incierto y/o ausencia de diagnóstico preoperatorio definitivo. Se practicó cirugía en 25/51 pacientes, habiéndose realizado 10 resecciones anatómicas y 15 resecciones atípicas o enucleaciones. No hubo muertes postoperatorias. Otros dos pacientes operados por probable hemangioma demostraron tener neoplasias malignas hepáticas primarias. En los 26 pacientes no resecados no se observaron complicaciones durante el seguimiento; en tres casos se detectó ensanche del hemangioma en el examen con ultrasonido, pero no se presentaron síntomas. Puesto que actualmente los hemangiomas cavernosos del hígado pueden ser diagnosticados con mayor certeza y puesto que su historia natural generalmente está libre de complicaciones es posible evitar la cirugía en la mayoría de los casos. Sin embargo, cuando se pretenda adoptar una política de no resección es esencial establecer el diagnóstico exacto para excluir la posibilidad de un cáncer primario o metastásico. La exploración y el tratamiento quirúrgicos debe permanecer limitados a los hemangiomas sintomáticos o complicados, y en ningún caso deben significar riesgo para el paciente.

---

Résumé De Janvier 1972 à Juin 1989, 51 patients ayant un hémangiome du foie (32 femmes et 19 hommes, âge moyen 35 ans) ont été examinés en vue d'une exérèse chirurgicale. Le diamètre de la lésion variait entre 5 et 20 cm (médiane = 8.5 cm). Neuf des patients avaient déjà été traités pour un cancer; 22/51 (43.1%) étaient symptomatiques alors que 29/51 (56.9%) étaient asymptomatiques. Chez 34/51 patients (66.7%), le diagnostic définitif d'hémangiome a été confirmé par scintigraphie et/ou échographie et/ou tomodensitométrie, alors que chez les 17 autres (33.3%), le diagnostic était uncertain. Les indications d'une résection les plus fréquentes étaient: la présence d'un angiome symptomatique, une masse symptomatique avec un diagnostic uncertain, et/ou absence de diagnostic définitif préopératoire. Vingt-cinq des 51 patients ont été opérés. Il y a eu 10 résections anatomiques et 15 résections atypiques ou énucléations. Il n'y a pas eu de mortalité postopératoire. Deux autres patients, traités pour ce que l'on soupçonnait être une probalbe hémangiome du foie, avaient en fait un cancer hépatique. Chez les 26 patients non résequés, il n'y avait pas eu de complication. Chez trois patients, on a mis en évidence une augmentation de volume par l'échographie, mais ces modifications ne s'accompagnait d'aucune symptomatologie. Comme on peut faire le diagnostic d'hémangiome carverneux du foie avec plus de fiabilité qu'avant, et comme on sait que leur histoire naturelle est généralement bénigne, on peut le plus souvent surseoir à l'exérèse chirurgicale. Cependant, il importe de toujours faire le diagnositc avec certitude, de façon à éliminer un cancer primitif ou sécondaire du foie.