Treatment of metastatic prostate cancer. Lessons from the androgen receptor

The exquisite hormonal dependence of prostate cancer continues to provide an opportunity and a challenge for oncologists. It is clear that future efforts in the laboratory should include determining the frequency and spectrum of AR mutations in AI prostate cancer, the development of more effective antiandrogens, and understanding in greater detail how the AR stimulates the growth of prostate cancers. These efforts may eventually lead to treatments that greatly reduce any stimulatory effects of the AR on prostate cells, possibly resulting in a significant improvement in disease-free survival and, perhaps in conjunction with other modalities, cure of some earlier stages of disease. And even for patients with advanced disease, because hormonal therapy is generally fairly well tolerated even in the typically older prostate cancer patient, defining the contribution of AR-mediated growth to AI disease will be critically important.     

Widespread arterial thrombosis in association with metastatic carcinoma--a case report

Inferential studies suggest that circulating insulin concentrations positively regulate leptin secretion by adipocytes. In humans, however, insulin requires prolonged periods of time, and relatively artificial set-ups before a relationship with leptin can be observed. In the present work, serum leptin concentrations were measured in five patients with insulinoma before and one month after surgery and in five control subjects matched by sex and body mass index (BMI). The control subjects presented a mean serum leptin concentration of 6.7+/-1.5 microg/l and a BMI of 24.9+/-1.1. The mean serum leptin concentration in patients with insulinoma was 11.8+/-3.1 microg/l (P < 0.05 vs controls), with a BMI of 26.3+/-1.9. After surgery, there was a non-significant reduction in BMI (25.8+/-1.7), and a clear reduction in serum leptin concentration (5.6+/-2.4 microg/l, P < 0.05 vs pre surgical values and no difference vs control subjects). The fasting area under the curve (AUC) of insulin concentration (in mU/l per 120 min) before surgery was 14421+/-4981 and after surgery was 1306-/+171 (P < 0.05). Before surgery, serum leptin concentrations significantly correlated with BMI (r = 0.71) and AUC of insulin (r = 0.82), a correlation that was lost after surgery. In conclusion, serum leptin concentrations are significantly elevated in patients with chronically high insulin levels due to insulinoma. After surgical treatment and normalization of insulin values, leptin levels return to normal.     

Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis

Osteomyelitis, or bone infection, is a major worldwide cause of morbidity. Treatment is frequently unsatisfactory, yet little is known about pathogenesis of infection. Plasma tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 concentrations were measured before and after lipopolysaccharide stimulation of whole blood from patients with bacterial and tuberculous osteomyelitis and from controls. Patients with bacterial and tuberculous osteomyelitis mounted an acute-phase response and were anemic and febrile. However, plasma IL-6 concentrations were significantly elevated in only tuberculous osteomyelitis patients (vs. controls, P < .05). IL-6 concentrations correlated with erythrocyte sedimentation rate, C-reactive protein level, and plasma albumin concentration, all acute-phase markers. There were no other correlations between cytokine concentrations and clinical data. Following ex vivo stimulation, TNF, IL-6, and IL-8 were secreted equally by patients and controls. In summary, tuberculous osteomyelitis is characterized by elevated systemic IL-6 concentrations associated with an acute-phase response. For further insight into immunopathology of osteomyelitis, studies on infected bone are required.     

Detection of sight-threatening diabetic eye disease

Blindness due to diabetes mellitus is potentially preventable in the majority of patient. Early detection of sight-threatening changes is associated with a better outcome, indicating the need to screen for retinopathy. At least 50% of diabetic patients do not attend a hospital, so that diabetologists and ophthalmologists are unable to screen the diabetic population comprehensively. Although in theory all patients has access to general practitioners, these may lack training or confidence to screen for retinopathy. Hospital based or community optometrists using direct ophthalmoscopy or slit lamps and technicians performing fundus photography are alternatives which may be more effective. Further studies are required to examine the effectiveness of optometry screening. Initial studies using fundus photography raised concerns about the sensitivity of the technique, but these have been partially addressed by improvements in methodology and technology. As well as technicological effectiveness, factors affecting patient uptake of screening services still need to be addressed.     

Interbacterial binding among strains of pathogenic and commensal oral bacterial species

OBJECTIVE: Family resources and coping skills are important to adaptation to pediatric chronic illness. Psychological and educational interventions have been found to enhance the coping skills of children with juvenile rheumatic disease (JRD) and their families. We examined the efficacy of a 3-day family retreat as a multidisciplinary, comprehensive treatment. METHODS: Children with JRD and their caregivers completed questionnaires assessing the children's behavioral and emotional functioning, pain, strain on caregivers' work and leisure activities, and caregivers' psychological distress before and 6 months after the family retreat. Principal caregivers were both parents for 16 children, mothers only for 10 children, and an aunt for 1 child. RESULTS: Improvements were found in children's emotional functioning, strain on caregivers' work, and strain on caregivers' leisure activities. Reductions in reported pain were not consistently revealed. CONCLUSIONS: Family retreats are an efficacious, multidisciplinary approach to helping families of children with JRD cope with the disease and its manifestations. Importantly, retreats offer a comprehensive intervention package that might not be available to families on an individual basis.     

First trimester isolated fetal nuchal lucency: significance and outcome

BACKGROUND: In this retrospective study the postoperative alteration of intraocular pressure after cataract extraction and posterior chamber lens implantation was analyzed statistically. The influence on intraocular pressure between different positions of the loops (sulcus versus bag) was compared. PATIENTS AND METHOD: The posterior chamber lens implantation was performed on 267 eyes with 129 sulcus implanted and 138 in-the-bag implanted intraocular lenses. The average age of the patients was 74.8 respectively 71.9 years, with an equal ratio of sex. In surgery the viscoelastic experimentation of the nucleus was done via corneoscleral cut. A x-crossed suture sealed the corneoscleral wound followed by subconjunctival injection of corticosteroids. The postoperative medication for 4-6 weeks consisted of a corticosteroid and antibiotic combination. RESULTS: The average intraocular pressure of the sulcus implanted respectively in the bag implanted intraocular lenses increased from 15.4 mm Hg respectively 15.9 mm Hg preoperatively to 16.3 respectively 15.8 mm Hg at the first postoperative day. After two months the intraocular pressure decreased to 14.6 respectively 14.1 mm Hg. That means a pre- to postoperative difference of -0.8 respectively -1.8 mm Hg. CONCLUSIONS: In summary both groups showed a slight decrease in average intraocular pressure after two months. In comparison to the sulcus implanted intraocular lens the decrease of intraocular pressure was more than 1 mm Hg in case of the in the bag implanted lens. This decrease was statistically significant but may be considered of less clinical interest.     

Oral immunization of mice with attenuated Salmonella typhimurium aroA expressing a recombinant Mycoplasma hyopneumoniae antigen (NrdF)

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia, a commercially expensive respiratory disease of swine. Salmonella typhimurium SL3261 was used as a live carrier of plasmid pKF1, which encodes a 15-kDa recombinant M. hyopneumoniae protein. This expressed recombinant protein consists of the carboxy-terminal 11 kDa of a 42-kDa M. hyopneumoniae NrdF ribonucleotide reductase R2 subunit protein. Rabbit anti-15-kDa serum was able to inhibit the growth of viable M. hyopneumoniae J in vitro. When used as a live oral vaccine, S. typhimurium SL3261(pKF1) induced a significant secretory immunoglobulin A immune response in the lungs of mice orally immunized against the M. hyopneumoniae antigen. Utilization of live oral vaccines expressing potentially protective M. hyopneumoniae proteins, such as the NrdF antigen, which can stimulate a lung mucosal response against surface-accessible proteins may provide a cost-effective alternative to the present control strategies used for porcine enzootic pneumonia.     

Normal findings in vulvar examination and vulvoscopy

Expression of chicken and rat liver bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, in Escherichia coli encountered two common problems: the chicken enzyme was liable to proteolysis and the rat enzyme was prone to form inclusion bodies. Reducing the rate of protein synthesis by lowering either growth temperature or isopropyl-beta-D-thiogalactopyranoside (IPTG) concentration alleviated these two problems. Growth at 22 degrees C was optimum for expression of both enzymes. The optimum range of IPTG concentration for expression was 0.1-1 microM for the chicken liver bifunctional enzyme and 10 microM for rat liver enzyme. The components of growth medium also influenced the production. Compared with Luria-Bertani medium, an enriched medium-tryptone-phosphate medium-tripled the production of the active enzymes. Addition of glucose (0.2%) doubled the expression level of active chicken liver enzyme, but reduced the production of active rat liver enzyme to half the maximal level, while the phosphate in tryptone-phosphate medium had no effect on the production of the two enzymes.     

Localization and characterization of the human ADP-ribosylation factor 5 (ARF5) gene

ADP-ribosylation factor 5 (ARF5) is a member of the ARF gene family. The ARF proteins stimulate the in vitro ADP-ribosyltransferase activity of cholera toxin and appear to play a role in vesicular trafficking in vivo. We have mapped ARF5, one of the six known mammalian ARF genes, to a well-defined yeast artificial chromosome contig on human chromosome 7q31.3. In addition, we have isolated and sequenced an approximately 3.2-kb genomic segment that contains the entire ARF5 coding region, revealing the complete intron-exon structure of the gene. With six coding exons and five introns, the genomic structure of ARF5 is unique among the mammalian ARF genes and provides insight about the evolutionary history of this ancient gene family.