C-Kit and Its Ligand Stem Cell Factor: Potential Contribution to Prostate Cancer Bone Metastasis

The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion.     

Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination

A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years.     

Feeding during acute diarrhea as a risk factor for persistent diarrhea

Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children.     

Role of Moraxella (Branhamella) catarrhalis as a respiratory pathogen in children

During a 12-month surveillance period in 1981-1982, Moraxella catarrhalis was detected in cultures from nasopharyngeal aspirates from 76 (17%) of 449 children hospitalized with middle or lower respiratory tract infection. Seroconversion to M. catarrhalis was positive in 4(5%) of the 76 patients with M. catarrhalis present in nasopharyngeal aspirates and in 4(1%) of 373 patients with a negative finding. Although children with respiratory tract infections were often colonized by the organism, this was rarely the infective agent of the middle or lower airways. Four of 8 patients with seroconversion to M. catarrhalis exhibited a concomitant RSV infection. The carriage of this species was more closely associated with parainfluenza virus infections. Serological responses to M. catarrhalis were not associated with acute otitis media, and were also rare in children with pneumonia. It is concluded that bronchopulmonary infections caused by M. catarrhalis are rare in children, and that M. catarrhalis aetiology need not be considered in the selection of antibiotics in cases of community-acquired pneumonia or other infections of the middle or lower respiratory tract affecting primarily healthy children.     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² [2 mg maximum] on day 1; dexamethasone 10 mg/m² days 1–5), and MTX (3.5 gm/m²) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.     

Prostate cancer diagnosis,staging and survival

Prostate cancer is the most common malignancy in men and the second most common cancer related death. Through research, we have found that African–American men and men with a family history of prostate cancer have a significantly higher risk of prostate cancer. In the 90's the mortality rate from prostate cancer decreased, presumably due to PSA testing. Patients with organ-confined tumors, particularly if they have a moderate Gleason score have an excellent chance of long-term survival with radical prostatectomy or external beam radiation therapy. Advances in detecting micrometastatic disease are needed to further impact on this disease.