Monotherapy in advanced prostate cancer: an overview

Prostate cancer is the second leading malignancy in men associated with an enormous research interest in all aspects of the disease. It is well recognized that the regulation of prostatic growth is a complicated biological process. Further more the androgenic dependence of the advanced prostate cancer is well know and in the last 50 years significant progresses regarding the principle of deprivation of androgens for the treatment of the disease occured. Prostate cancer is now diagnosed in earlier stages and treatment results in increased potential for cure or extension of overall survival. Unfortunately, every treatment for prostate cancer has adverse effects with negative impact in health-related quality of life. Surgical or pharmacological castration has a significant negative impact on quality of life in patients with prostate cancer (loss of sexuality, osteoporosis, and loss of muscle mass, e.g.). Antiandrogen monotherapy is considered to be a treatment in well-informed patients who wish to remain sexually active, can be administered orally, and is well tolerated by patients with prostate cancer. This review is focused on antiandrogen monotherapy in the treatment of advanced prostate cancer.     

Breast carcinoma metastasis to the orbit and paranasal sinuses: a case report

This is the case of a 34 years old female patient, with known history of disseminated, invasive, ductal adenocarcinoma, grade II, of the left breast, who presented with two distinct localizations of metastasis affecting the orbits. One in the right orbit and a second one in the frontal sinuses, the latter infiltrating the cognate ethmoid, exerting pressure on the inner wall of the left orbit. We present the symptoms, the ophthalmic signs and the imaging techniques that aided the localization of these metastasis, while literature review shows that such combination is rare.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

Brucella melitensis infection stimulates an immune response leading to Kikuchi-Fujimoto disease

A 43-year-old Greek cattler with a history of brucellosis three months previously for which he was treated with sulfonamides for three weeks, was admitted to the hospital complaining of fever, arthralgias, night sweats, painful cervical and axillary lymph nodes as well as a weight loss of 8 kg in the previous four months. Since microbiological and serological studies did not give a specific diagnosis, an open cervical lymph node biopsy was performed. The histological examination revealed Kikuchi-Fujimoto disease. The etiology of the disease is unknown but viral, bacterial, protozoal and neoplastic as well as physicochemical agents may stimulate a particular immune response leading to Kikuchi-Fujimoto disease. Hereby, we present a case in which Kikuchi-Fujimoto disease followed brucella melitensis infection. This association permits us to hypothesize that the initial brucella melitensis infection three months previously triggered an immune response leading to Kikuchi-Fujimoto disease. The association of the disease with brucellosis is very important since these two entities share some similar characteristics, with brucellosis being relatively common in Europe. To our best knowledge, in the English language bibliography, this is the first reported case worldwide, though another similar case was described in the Spanish literature ten years ago.     

Umbilical cord plasma interleukin-6 and fetal growth restriction in preeclampsia: a prospective study in Norway

OBJECTIVE: To study the association between umbilical plasma levels of interleukin-6 (IL-6) in relation to fetal growth in subgroups of preeclampsia, and in control pregnancies. METHODS: Umbilical cord plasma was collected from 12,804 consecutive births. A total of 271 singleton cases of preeclampsia were identified, and classified as mild or severe, and as disease with early or late onset. As controls, 611 singleton pregnancies without preeclampsia were selected, and the ratio between observed and expected birth weight was used as a measure of fetal growth. In the analysis, we also included maternal smoking during pregnancy. Umbilical cord plasma IL-6 concentration was measured with an IL-6 bioassay. Comparing controls with subgroups of preeclampsia (severe and early onset), this study had a statistical power of 90% to detect a difference in cord IL-6 of 10 pg/mL. RESULTS: In severe preeclampsia, cord plasma IL-6 concentration was lower than among controls (P <.001), and there was a sharp decrease in cord plasma IL-6 with decreasing birth weight ratio (P trend <.001). By further dividing the preeclampsia group into early or late onset, the strong association between low IL-6 levels and low birth weight ratio appeared to be present mainly in early-onset disease. These results were not confounded by maternal smoking. CONCLUSION: Restricted fetal growth related to preeclampsia is associated with reduced umbilical cord plasma IL-6 concentration in cases with early-onset disease. In these cases, fetal growth restriction could be mediated by impaired trophoblast function.     

TUBULAR PROTEINURIA AFTER PERINATAL HYPOXIA

ABSTRACT. Milt7eacute;nyi, M., Pohlandt, F., Bóka, G. and Kun, E. (2nd Department of Paediatrics, Semmelweis University, Medical School, Budapest, Hungary, and the Section of Neonatology, Centre of Paediatrics, University of Ulm, Federal Republic of Germany). Tubular proteinuria after perinatal hypoxia. Acta Paediatr Scand, 70:399, 1981.–Urinary total protein (UTP) and urinary protein pattern have been studied in 23 newborn infants with Apgar scores ±S3 at one minute or acidosis (pH ±7.15) on the first day. On the first and second day UTP excretion was increased in 13 out of 18 patients. At this time the excretion of low molecular weight microproteins (T-4 and T-5) was elevated in 12 patients without increased plasma urea concentration in any case. The increased excretion of the smallest microproteins T-4/T-5 is an early sign of an impaired tubular function.     

Integrin receptors in primary lung cancer

In the present review recent data regarding the role of integrins--an important category of adhesion molecules mediating interactions among cells and components of the extracellular matrix--in lung cancer development is discussed. Investigations have shown that down-regulation of alpha3 integrin subunit may contribute to enhanced tumorigenicity of c-myc-overexpressing small cell lung carcinoma, while the loss of an integrin expression is correlated with recurrence in node-negative lung carcinoma. Increased expression of alpha1beta1 and alpha2beta1 integrins have been shown to be positively correlated with increased metastatic ability in squamous cell carcinoma. alpha3beta1 integrin is a most critical integrin for pulmonary development and epithelium integrity and its reduced expression in small cell lung cancer is probably related to the increased aggressiveness of this type. Pulmonary cancer cells generally express fewer integrin receptors than the normal epithelium. Additionally, since the ability of malignant cells to interact with extracellular matrix components is thought to be important, integrin dependent migration of lung cancer cells is a crucial process.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.