The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Prospective comparative study of cefotetan with piperacillin for prophylaxis against infection in elective colorectal surgery

This study compared one dose of cefotetan with three doses of piperacillin as prophylaxis against wound infection in 153 patients undergoing elective colorectal surgery. The patients were randomized into two groups: the first received 2 g cefotetan intravenously with induction of anaesthesia (n = 75), and the second received three doses of 2 g piperacillin (n = 78). Wound infection was defined as the presence of an abscess or discharging pus from the wound. In the cefotetan group there were 14 (19%) wound infections and 13 (17%) in the piperacillin group. There were three septic deaths, one in the cefotetan group and two in the piperacillin group. Both groups were comparable with regard to age, sex, nature of pathology and pre- and perioperative risk factors. No significant haematological or biochemical abnormalities were detected. The only adverse reaction was one patient who had an allergic reaction (rash) to piperacillin. These data suggest that single-dose cefotetan is as effective as triple-dose piperacillin in prophylaxis against infection in elective colorectal surgery.     

Beta carotene uptake into atherosclerotic plaque: Enhanced staining and preferential ablation with the pulsed dye laser

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430–530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of β-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous β-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. β-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following β-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in β-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model β-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation. © 1993 Wiley-Liss, Inc.     

The effect of currently available contact lens disinfection systems on Acanthamoeba castellanii and Acanthamoeba polyphaga

Contact lens disinfection systems were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Amoebae were inoculated into commercially available contact lens cleaning and soaking solutions. At intervals varying from 30 minutes to 24 hours, solutions were filtered. The filters were removed and cultured for Acanthamoeba organisms. Striking differences were observed in the abilities of the different disinfecting solutions to kill the organisms. Solutions containing chlorhexidine were effective at very short exposure times. Solutions containing benzalkonium chloride required slightly longer exposure times but were faster than solutions containing only thimerosal. Solutions containing sorbate, polyaminopropyl biguanide, or polyquaternium-1 were not effective at killing Acanthamoeba organisms in the time allotted for the experiment. Solutions containing hydrogen peroxide were quite effective if the agent was not prematurely catalyzed. A. polyphaga generally required longer exposure to disinfectants than did A. castellanii for complete inhibition to occur.     

Ecology of a Southern Ohio stream receiving fly ash pond discharge: Changes from acid mine drainage conditions

Prior to 1975, Stingy Run was a third-order tributary of Kyger Creek, which empties into the Ohio River at Mile 260 (Gallia County, Ohio). Both streams drained strip mine refuse areas and physicochemical measurements indicated acidicmine drainage conditions (e.g., low pH). A depauperate macroinvertebrate community, dominated by a few acid-tolerant taxa, was found in both streams and no fishes were collected. In 1974, Stingy Run was impounded to form a fly ash pond which contains fly ash sluiced from Ohio Power Company's General James M. Gavin coal-fired power plant. Physicochemical and biological sampling during 1975–1986 indicated marked changes in the aquatic ecology of Stingy Run between 1) pre-impoundment and post-impoundment conditions; and 2) effluent pH control treatments after impoundment. Fly ash discharge eliminated acidicmine drainage characteristics in Stingy Run and lower Kyger Creek. After impoundment, net spinning caddisflies and a few dipteran taxa dominated the Stingy Run benthic community, reflecting changes in functional niches likely due to improved habitat and greater food availability. Replacement of acid feed by CO₂ injection for effluent pH control and changes in ash pond chemistry occurred concomitant with elimination of a substrate floc; increased species richness and densities of invertebrates were subsequently observed. In Stingy Run, species richness and diversity of fishes increased from 1983 to 1986, reflecting improved water quality and increased benthic production after impoundment. Many of these fishes are opportunistic feeders on drifting insects.     

Phase I/II trial of dipyridamole, 5-fluorouracil,leukovorin, and mitoxantrone in metastatic breast cancer

Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m² by mouth every 6 h (700 mg/m²/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m² was given intravenously immediately prior to 5-FU 375 mg/ m² intravenously on days 1–5. Mitoxantrone 6 mg/m² was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m² days 1–2, 5-FU 375 mg/m² days 1–2, mitoxantrone 6 mg/m² on day 2, and dipyridamole 175 mg/m² every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.     

CD4-specific monoclonal antibody can prolong cardiac allograft survival without T-cell depletion

Current immunosuppressive regimens for clinical transplantation are immunologically non-specific, are associated with acute and chronic toxic side-effects [1] and are unable to prevent chronic graft loss in a significant proportion of patients. Additionally, new and increasingly powerful drugs are being introduced to induce non-specific immunosuppression, and therefore this is likely to be followed by an increase in related complications such as the induction of cancers. Hence, there is a need for an alternative approach. It has been shown that long-term survival of murine cardiac grafts can be induced by the monoclonal antibody YIS 191 that depletes CD4 ⁺T cells in vivo [2]. In this study, we have investigated the ability of a non-depleting antibody to produce better graft survival.     

Physical symptoms/side effects during breast cancer treatment predict posttreatment distress

Background: Studies suggest that the period following completion of treatment can be distressing for cancer patients. One potentially important predictor of distress is physical symptoms/side effects during treatment.Purpose: A longitudinal, observational design was used to examine whether the number of physical symptoms/side effects experienced during treatment was a correlate of cancer-related distress and general distress 4 months after treatment completion, as measured by the Impact of Events Scale and the Mental Health subscale of the Short Form-36, respectively.Methods: Participants were 151 women who had completed chemotherapy and/or radiotherapy for ductal carcinoma in situ or stage 1 or 2 breast cancer. Hierarchical multiple regression was conducted with relevant sociodemographic, clinical, and psychiatric variables entered as controls.Results: Greater physical symptoms/side effects predicted greater total cancer-related distress, intrusive thoughts, and general distress. Physical symptoms/side effects did not significantly predict avoidance. Follow-up analyses indicated that the relationship between physical symptoms/side effects and general distress was mediated by both total cancer-related distress and intrusive thoughts.Conclusions: These results suggest that patients who experience greater physical symptoms/side effects during treatment are at greater risk for later cancer-related distress and, in turn, general distress. Future research should evaluate whether early intervention with these patients is effective in preventing or reducing distress in the posttreatment period. This work was supported by a grant from the National Cancer Institute (5R01 CA082822).     

Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.