Paracetamol (acetaminophen) rescues cognitive decline, neuroinflammation and cytoskeletal alterations in a model of post-operative cognitive decline (POCD) in middle-aged rats.

Post-operative cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of pain in elderly is complicated because analgesic opiates elicit major side effects. In contrast, paracetamol (acetaminophen) has shown analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of paracetamol, compared to the opioid analgesic buprenorphine, in a model of POCD by investigating cognitive decline, allodynia, peripheral and hippocampal cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received isoflurane anaesthesia. We demonstrated that cognitive decline and increased allodynia following surgery was prevented in paracetamol-treated animals, but not in animals which were exposed to anesthesia alone or underwent the surgery and received buprenorphine. Behavioral alterations were associated with different peripheral cytokine changes between buprenorphine and paracetamol treated animals. Buprenorphine showed no central effects, while paracetamol showed modulatory effects on hippocampal cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of paracetamol as first-choice analgesic in POCD.

Selection of pre-operative haematobiochemical parameters for the identification of patients 'at risk of infection' undergoing surgery for gastro-intestinal cancer.

Sixty-three patients were given a complete laboratory screening before undergoing surgical treatment for cancer of the digestive tract. The values of all these parameters were correlated with the incidence of postoperative infections, with the aim of identifying those markers which could be useful for the pre-operative selection of the patients at risk of infection. Patients who developed postoperative infections showed a significant pre-operative reduction of total serum proteins (P less than 0.02), albumins (P less than 0.02), beta-globulins (P less than 0.01) and C3c (P less than 0.05), while alpha 1-globulins were slightly, but not significantly, increased. The possible clinical applications of these parameters, to develop a predictive model which may help identify the patients at risk of infection, are discussed.

A cohort study of workers employed in a refractory brick plant.

A mortality study was carried out on a cohort of workers who were exposed to silica dust in a refractory brick plant. The cohort was divided into two groups: workers with and without silicosis, and their mortality was contrasted with the death rate of Genova from 1960 to 1979. Results show an increased risk for laryngeal tumors (3 obs., 0.44 exp., SMR = 682), nonmalignant respiratory disease (16 obs., 3.2 exp., SMR = 500), and cardiovascular diseases (19 obs., 11 exp., SMR = 173) among silicotics. The mortality rate for lung cancer showed an increase for the cohort of workers as a whole (11 obs., 6 exp., SMR = 183). The almost double overall mortality observed in silicotic subjects raises some doubts about the validity of other proportional mortality studies that showed no excesses for workers in these industries.

Hypercoagulable state induced by cytostatic drugs in stage II breast cancer patients.

An increased incidence of thromboembolic complications occurring in cancer patients during chemotherapy was recently reported. In view of this report, a study in 49 patients receiving adjuvant chemotherapy for Stage II breast cancer was begun in order to determine the effect of antineoplastic drugs on coagulation factors and platelet function. Among the coagulation factors, a significant decrease of thrombin time and partial prothrombin time was observed, whereas platelet function tests were unchanged. This finding suggests a trend towards hypercoagulability induced by chemotherapy. This effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis.

Cyclosporin A serum and blood levels in marrow graft recipients: correlation with administered dose, serum creatinine and graft-versus-host disease.

23 patients undergoing marrow transplantation for leukemia or aplastic anemia were given cyclosporin A (CyA) for graft-versus-host disease (GvHD) prophylaxis. A radioimmunoassay was used to monitor CyA serum levels in 13 patients and whole blood levels in 10. Serum creatinine levels were recorded daily until day 30 and then weekly. The severity of acute GvHD was recorded daily for a total of 1,738 patient days. CyA dose was then correlated with CyA serum or blood levels, serum creatinine levels and severity of acute GvHD. The daily dose of administered CyA correlated with serum CyA levels (p = 0.001) but not with whole-blood CyA levels. The cumulative CyA dose correlated with serum creatinine. There was an inverse correlation between the daily CyA dose and the severity of acute GvHD (p = 0.05). On the other hand the total amount of CyA given within 10 days after bone marrow transplantation had no influence on the severity of acute GvHD developing after day 10. Serum and whole-blood levels did not correlate with severity of GvHD nor with creatinine levels. The results of this study point out the nephrotoxicity of CyA, and a low GvHD score with high doses of administered CyA, at least on a daily basis. Serum but not blood levels reflect the dose of CyA given, but are not correlated with nephrotoxicity or GvHD.