Impact of elective resection on plasma TIMP-1 levels in patients with colon cancer.

OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106 ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant (P<0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively.

Ranitidine improves certain cellular immune responses in asymptomatic HIV-infected individuals.

Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28 days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection. Spontaneous and in vitro interleukin-2- and interferon-alpha-stimulated natural killer cell activity improved in the ranitidine-treated patients in contrast to a decrease in nontreated patients (#p less than 0.03, #p less than 0.01, #p less than 0.02 between groups, respectively). Furthermore, T-cell blastogenesis to phytohemagglutinin stimulation and soluble interleukin-2 receptors in serum increased in ranitidine-treated patients compared with nontreated patients (#p less than 0.01). However, ranitidine treatment did not change CD4+ cell counts. Although the significant improvement in immunocompetence shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals.