Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.     

Amylase production of Streptomyces rimosus TM-55 and their 2-deoxyglucose resistant mutants

Human papillomavirus (HPVs) adenovirus and simian virus 40 (SV40) are small DNA viruses which can show oncogenic activity. Although not otherwise related, all three have adopted very similar strategies to deregulate cell growth; each virus encoding oncoproteins which interact with the same cellular targets. Of particular interest are the interactions with the cell encoded pRB and p53 proteins, products of tumour suppressor genes. Somatic mutation results in the loss of the pRB and p53 function in many cancers and the contribution of the viruses to tumour development appears to reflect their ability to inactivate these cellular proteins. Both pRB and p53 negatively regulate progress through the cell cycle and the action of the viral proteins has highlighted the central importance of these tumour suppressor proteins in maintaining normal cell growth.     

Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.     

Quality of life of patients with gastric adenocarcinoma after curative gastrectomy

Quality of life (QOL) was evaluated in 162 patients having radical gastrectomy for cancer. The results showed that more than half of the patients had a good appetite; they consumed a normal diet and a normal volume of food. Approximately 60% of the patients had weight loss of more than 5 kg. Patients who underwent a total gastrectomy had poor tolerance of normal food and frequent eating and body weight loss versus those who had a subtotal gastrectomy. Patients who underwent Billroth II reconstruction after a distal subtotal gastrectomy lost more body weight than those with a Billroth I anastomosis. The extent of lymphadenectomy did not influence the QOL. Patients under 65 years of age had a better QOL. Nearly all patients had normal work and daily living activities. Some patients appeared to lack energy or had a period of anxiety or depression. These data indicate that radical gastrectomy can be performed with an acceptable QOL for a potentially curable gastric carcinoma.     

Dietary guidelines for Americans: an historical perspective

The laminin peptide fragments GYIGSR-NH2 and CDPGYIGSR-NH2 are known to bind to a 67-kDa laminin receptor. This receptors is understood to be expressed at higher than normal levels in malignant tumor cells, particularly those of breast and colon carcinomas. Peptides DTPA-GYIGSR-NH2 (1), DTPA-(GYIGSR-NH2)2 (2), DTPA-CDPGYIGSR-NH2 (3), DTPA-(CDPGYIGSR-NH2)2 (4), and negative control DTPA-GAGAGA-NH2 (5) were prepared by solid-phase peptide synthesis. All five DTPA-conjugated peptides were subsequently radiolabeled with 111In and their tissue distribution evaluated in mice bearing C3H tumors. 111In-3 and 111In-4 showed the highest specific tumor localization. These preliminary data support further study of radiolabeled petide fragments for the potential detection of malignant tumors of the breast and other organs.     

In vitro bioartificial skin culture model of tissue rejection and inflammatory/immune mechanisms

We hypothesized that an in vitro bioartificial skin rejection model using living LSEs grown in tissue culture could be developed for the study of autologous, allogenic, and/or xenogeneic inflammatory/immune mechanisms and topical immunosuppressive drugs. Human fibroblasts were mixed with type 1 rat-tail collagen to form a matrix (4 to 5 days), on which human keratinocytes were seeded. After a keratinocyte monolayer formed, CT cultures were raised to the air-liquid interface for continued growth. In the REJ LSE model, immunocytes isolated from human blood were seeded on top of the NHEK monolayer at the time of air-lifting. Thickness measurements of the acellular keratin and keratinocyte layers, and nuclear/cytoplasmic ratios, in both CT and REJ were made using digital image analysis. Immunostaining with anticytokeratin demonstrated a viable, keratin-producing epidermal layer; staining with anti-TGF-beta suggested a role for this cytokine in the rejection or wound-healing process. The LSE appeared histologically similar to normal human epidermis. Immunocytes added to the REJ cultures caused an obvious rejection response and were clearly identifiable in the gels as CD45+ staining cells. The LSE model appears promising for the study of immune/inflammatory mechanisms, thermal injury, screening antirejection agents that might be applied topically and as an in vitro replacement for skin graft studies in animals.