CD4 responses to conserved HIV-1 T helper epitopes show both negative and positive associations with virus load in chronically infected subjects

Characterization of immune responses to immunodominant CD4 epitopes in HIV-1 that are associated with control of HIV infection could be used to strengthen the efficacy of polyepitope HIV vaccines. We measured both the proliferative and the CD4 interferon (IFN)-gamma and interleukin (IL)-2 cytokine responses specific for 11 previously identified HIV-1 T helper epitopes in 10 HIV-infected non-progressors (LTNPs) (infected for a median of 15 years with a stable CD4 count of >500 cells x 10(6)/l), and seven slow progressors (SPs) (infected for a median of 15 years with a CD4 count that had declined to <500 cells x 10(6)/l). Both groups were antiretroviral treatment-naive at the time of evaluation. The median virus load of SP group was higher than that of the LTNP group (P = 0.0002). The CD4 response to a peptide pool representing all potential CD4 Gag epitopes and to Gag p24 protein was also studied. Compared to SPs, LTNPs had higher numbers of Gag-specific IFN-gamma+IL-2+ CD4s (P = 0.0059). The Gag-specific cytokine and proliferative responses correlated inversely with virus load (P = 0.03 and 0.0002, respectively), highlighting the potential importance of this response in immunity to HIV. A direct correlation was noted between proliferation and the Gag-specific IL-2 (P = 0.0053) rather than IFN-gamma response (P = 0.1336), demonstrating that the proliferation assay reflected the IL-2 rather than the IFN-gamma secreting capacity of CD4 cells. Several subjects with diverse class II DRB1 alleles responded, confirming the 11 selected peptides to be both antigenic and conserved. CD4 cytokine responses to one Gag and two conserved Pol peptides correlated negatively with virus load. The cytokine response to two additional Pol peptides correlated positively with virus load. The data indicate that there is not an absolute correlation between the CD4 immune response to conserved and broadly antigenic helper T cell epitopes in HIV non-progression.     

Rectal cancer in the Kingdom of Saudi Arabia: the King Faisal Specialist Hospital experience

BACKGROUND: No survival data have yet been published from the Kingdom of Saudi Arabia for patients with rectal cancer. The present paper reports experience with these patients over an 8-year period. METHODS: All patients referred to the King Faisal Specialist Hospital (KFSH) between March 1990 and February 1998 for the primary management of rectal cancer were entered into a computerized database. Prior to 1993 patients did not receive adjuvant therapy. Kaplan-Meier survival curves and the log-rank test were used to compare outcome data. RESULTS: There were 70 men (average age: 55.6 years) and 75 women (average age: 52.8 years). Twelve per cent of patients admitted a family history of colorectal carcinoma (CRC). Twenty-seven per cent of tumours were circumferential. Most tumours were larger than 4 cm and the lowest edge of the majority of tumours was less than 6 cm from the anal verge. Fifty-four per cent of tumours were fixed; 69% of patients received either pre-operative or postoperative radiotherapy. A total of 106 patients underwent 'curative' surgery. Equal numbers of patients had abdomino-perineal resection (APR) and anterior resection (AR) of the rectum. Thirty-five patients received blood peri-operatively (APR, 34%; AR, 12%). Major anastomotic leakage following AR occurred in two patients. Two patients died within 30 days of surgery. Ten patients were lost to follow-up. Following curative AR, eight patients had a distal resection margin of < 2 cm and two patients (Dukes' C) developed local recurrence (25%); 37 patients had a margin > 2 cm and seven developed local recurrence (18.9%). A total of 48 patients underwent curative APR, and four patients developed local recurrence (8.3%). Overall local recurrence was tumour stage-dependent (Dukes' B, 8.8%; Dukes' C, 29.3%). Recurrence was local in 13 patients. Pre-operative radiotherapy seemed to reduce average tumour size (3.6 vs 4.3 cm). The crude overall 5-year survival rate was 39%. The 5-year survival rate for patients with Dukes' stage C cancers following 'curative' surgery was 25%. CONCLUSION: Curative surgery can be performed with a relatively low requirement for blood transfusion, a low mortality and morbidity, and comparable outcomes to Western studies in spite of the large, low and often advanced stage of the tumours managed. Local recurrence rates following curative resection and re-anastomosis for low rectal cancers may be reduced by resisting patient pressure to avoid stomata.     

Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.

PURPOSE: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. PATIENTS AND METHODS: We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. RESULTS: Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. CONCLUSION: Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.     

Two cases of dermatoses koebnerizing within fields of previous radiotherapy

We describe two patients with newly diagnosed dermatoses localizing to the radiotherapy field following treatment for breast cancer. Patient 1 was a 53‐year‐old woman who developed bullous morphoea on her left breast two years after radiotherapy. Patient 2 was a 43‐year‐old woman who developed urticaria pigmentosa on her right breast eight months after radiotherapy and similar lesions gradually developed beyond the radiotherapy field. Both patients experienced a significant delay in diagnosis due to diagnostic confusion and concern over breast cancer recurrence. Irradiated skin demonstrates gradual and sustained alterations in fibrosis due to the production of long‐lived cytokines and chemokines. These changes can induce a koebnerizing response in conditions such as morphoea and urticaria pigmentosa. We explore the mechanisms behind radiotherapy‐induced skin changes, and highlight the potential for radiotherapy to exacerbate or unmask underlying dermatoses and systemic disease in the months and years following treatment.     

Educating Women for HIV Prevention: Does Exposure to Mass Media Make Them More Knowledgeable?

Mass media is an important vehicle for health promotion in developing countries. In Bangladesh multiple media campaigns are being carried out to educate people about HIV/AIDS. We examined the extent of HIV/AIDS knowledge and the association of exposure to mass media among women in Bangladesh. The Bangladesh Demographic and Health Survey (BDHS) provides data for this article. We found that media exposure (combined index of television, radio, and newspaper) was a highly significant predictor of women's knowledge about HIV and AIDS. Other significant predictors of HIV knowledge include women's education, age, employment, and urban residence.