A methodology for using Lambda phages as a proxy for pathogen transmission in hospitals.

BACKGROUND: One major concern in hospitalized patients is acquiring infections from pathogens borne on surfaces, patients, and healthcare workers (HCWs). Fundamental to controlling healthcare-associated infections is identifying the sources of pathogens, monitoring the processes responsible for their transmission, and evaluating the efficacy of the procedures employed for restricting their transmission. AIM: To present a method using the bacteriophage Lambda (λ) to achieve these ends. METHODS: Defined densities of multiple genetically marked λ phages were inoculated at known hotspots for contamination on high-fidelity mannequins. HCWs then entered a pre-sanitized simulated hospital room and performed a series of patient care tasks on the mannequins. Sampling occurred on the scrubs and hands of the HCWs, as well as previously defined high-touch surfaces in hospital rooms. Following sampling, the rooms were decontaminated using procedures demonstrated to be effective. Following the conclusion of the simulation, the samples were tested for the presence, identity, and densities of these λ phages. FINDINGS: The data generated enabled the determination of the sources and magnitude of contamination caused by the breakdown of established infection prevention practices by HCWs. This technique enabled the standardized tracking of multiple contaminants during a single episode of patient care. Unlike other biological surrogates, λ phages are susceptible to common hospital disinfectants, and allow for a more accurate evaluation of pathogen transmission. CONCLUSION: Whereas our application of these methods focused on healthcare-associated infections and the role of HCW behaviours in their spread, these methods could be employed for identifying the sources and sites of microbial contamination in other settings.

Restoration of localized severely atrophic maxillary ridge: case report.

A procedure is described whereby a patient with a highly localized atrophic maxillary ridge has had the deformity corrected by utilizing a combination of a block of corticocancellous bone and a barrier membrane.

Structuring training goals for psychodynamic psychotherapy.

A multiaxial model that structures educational goals for psychodynamic psychotherapy has been developed. It specifies core aspects of psychodynamic psychotherapy, clusters them in categories that further define and link related areas, and presents a sequence that enables educators and students to focus on training goals in a consistent progression. This model has been used by the Director of Education as a basis for developing the curriculum, by students as a way of focusing learning and giving perspective to current work, and by supervisors to link individual teaching to the goals of the training program. This method has enhanced consistency, clarity, and efficiency in the psychotherapy program.

A phase II trial of piroxantrone in endometrial cancer: Southwest Oncology Group study 8918.

A phase II trial of the new anthrapyrazole piroxantrone was carried out by the Southwest Oncology Group in patients with advanced metastatic or recurrent endometrial cancer. A two-stage statistical design targeted accrual of 20 eligible patients. The starting dose of piroxantrone was 150 mg/m2 in patients without prior radiation therapy (RT) and 120 mg/m2 in patients with prior RT. There were 15 eligible patients, six of whom had received prior hormonal therapy while nine patients had not received prior hormonal therapy. Eight patients had received prior RT while seven patients had not received any prior RT. One to seven cycles of piroxantrone were administered. Dose escalation was feasible in four patients. No grade 5 toxicity was experienced by any patients. Most of the grade 4 (granulocytopenia in one) and grade 3 (leukopenia in three, granulocytopenia in three, anemia in two and thrombocytopenia in one) toxicity was related to myelosuppression. Grade 3 non-hematologic toxicities were nausea, fatigue and SGOT elevation. There was one partial response for a response rate of 7% (95% CI 0.2-32%) and median survival was 11 months (95% CI 3-13 months). The study was prematurely terminated due to lack of patient accrual.

Intraperitoneal mitoxantrone or floxuridine: effects on time-to-failure and survival in patients with minimal residual ovarian cancer after second-look laparotomy--a randomized phase II study by theSouthwest Oncology Group.

A randomized phase II study of intraperitoneal (ip) mitoxantrone or floxuridine (FUDR) was performed for the treatment of minimal residual epithelial ovarian cancer found at second-look laparotomy after initial platinum-based chemotherapy. Entry was to take place within 30 days of reassessment laparotomies, with documentation of peritoneal metastases either microscopic or gross with cytoreduction to less than or equal to 1 cm in largest diameter. Patients were stratified by the site of the largest disease present (microscopic to 0.5 cm maximum diameter versus greater than 0.5 to 1 cm maximum diameter), by time of registration (< 14 days versus up to 30), and by serum CA-125 (< or = 35 versus >35 units/ml) prior to randomization to either ip mitoxantrone 10 mg/m2 every 2 weeks X 9 or ip floxuridine (FUDR) 3 g (total dose)/ day X 3 days every 3 weeks X 6 cycles. Implantable ip systems and 1.5-2 liters of normal saline were used to deliver the drugs of 83 patients registered between December 1988 and January 1994; there were 6 pathology exclusions and 9 surgical exclusions, and 1 nonevaluable patient for a total of 39 evaluable on mitoxantrone and 28 on FUDR being evaluable. FUDR is the choice for further study because of a progression-free survival exceeding 15% at 1 year over mitoxantrone and a median overall survival of 38 months. It should be emphasized again that the goal of a randomized phase II selection design is to select a winner for phase III testing should there be a substantial difference between the treatments with respect to the primary endpoint. Comparative conclusions between the treatment arms should not be attempted due to the inherently much smaller sample sizes. This should reemphasize the limitations in a comparison of efficacy; however, the toxicologic differences still emerge quite clearly.

Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons.

The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 microgram/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%.

High-risk germ cell tumors in men. High response rate and severe toxicity with cisplatin, vinblastine, bleomycin, and etoposide.

BACKGROUND: In an attempt to improve the complete remission and cure rate of advanced, bulky, high-risk germ cell cancer in men, a "high-dose" cisplatin, vinblastine, bleomycin, and etoposide (PVeBV) regimen was introduced. METHODS: Ten men with biopsy-proven germ cell tumors who had one or more poor prognostic features were treated with PVeBV. RESULTS: Six of the 10 had complete remissions and are long-term survivors. The most devastating toxicity, which resulted in the death of three patients, was progressive respiratory failure. It was postulated that renal tubular injury prolonged the renal clearance of bleomycin, intensifying the patient's pulmonary exposure to this drug and increased the susceptibility to pulmonary injury at lower than expected cumulative doses of bleomycin. CONCLUSIONS: Modifications of the regimen to reduce toxicity without diminishing the efficacy should be considered before PVeBV is adopted for general use.

Acute toxicity of a nuclear magnetic resonance cerebral blood flow indicator in cats.

We studied trifluoromethane as a potential gaseous indicator in nuclear magnetic resonance measurements of cerebral blood flow. We considered the effects of trifluoromethane on cerebral blood flow in 17 cats and on the electroencephalogram and electrocardiogram in nine cats and compared these with the effects of the more toxic compound chlorodifluoromethane in five cats. Inhaled at 60%, trifluoromethane had no effect on cerebral blood flow, the cerebral metabolic rate for oxygen, or oxyhemoglobin content. At 70%, trifluoromethane sensitized the cats' hearts to epinephrine, but to a much lesser degree than 40% chlorodifluoromethane, and produced only moderate changes in cerebral electrical activity as measured by the electroencephalogram. We found trifluoromethane to be suitable for use in animals, but its toxicity needs to be studied further before it can be used in humans for the measurement of cerebral blood flow.

The relationship of alprazolam dose to steady-state plasma concentrations.

Alprazolam is a widely used antianxiety agent, yet relatively little is known about the relationship between chronic oral doses and steady-state plasma levels. This study examines the relationship over a wide range of therapeutic doses. We conducted a parallel, double-blind, placebo-controlled study in 36 patients with agoraphobia with panic attacks, or panic disorder with limited phobic avoidance based on DSM-III criteria. Patients received alprazolam (N = 25) or placebo (N = 11) beginning at 1 mg/day and increased weekly until either a maximum tolerated dose or 10 mg/day was achieved. Dosages were then gradually tapered according to a predetermined schedule. The entire study period lasted 14 weeks. Laboratory and clinical assessments were conducted weekly. Doses up to 6 mg/day were tolerated by 80% of patients on alprazolam and doses of 10 mg/day were tolerated by 40% of patients. Twenty-seven percent of the placebo patients reached 10 tablets/day. In the alprazolam group, the principal cause of intolerance was sedation. Throughout the study no significant changes in vital signs or laboratory parameters were observed. Steady state alprazolam, 4-hydroxy alprazolam, and alpha-hydroxy alprazolam plasma levels were linearly related to dose. A 1 mg dosage increment produced, on the average, a corresponding 10 ng/ml increase in steady state level of the parent drug. Significant response was observed in subjects who achieved concentrations greater than 20 ng/ml, with a maximum of 81% of the samples classified as responders within the 60 ng/ml and above group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of alcohol upon arrhythmias following nonpenetrating cardiac impact.

The purpose of this study was to determine if alcohol worsens arrhythmias produced by nonpenetrating cardiac impact. Twenty-three dogs were studied. Twelve underwent nonpenetrating cardiac impact alone at 12 m/sec with a contact compression of 2 cm. Eleven underwent cardiac impact after having received intravenous alcohol (blood level of 197 +/- 37 mg/100 ml) (mean +/- SD). Three dogs experienced ventricular fibrillation immediately after impact and died: of these, two underwent impact alone and one underwent impact following ethanol. These three dogs were eliminated from the study. All of the dogs had some form of complex arrhythmia during the first 10 minutes of observation, the average cumulative duration of which during the first 10 minutes following trauma was greater among dogs that received ethanol. No complex arrhythmias other than ventricular premature contractions or ventricular tachycardia were observed after the first 10 minutes following impact. During the first 2 hours of observation following cardiac impact, dogs that received alcohol before trauma showed more single premature ventricular contractions (p less than 0.03), couplets (p less than 0.01), triplets (p less than 0.02), runs of 4-20 beats (p less than 0.05), and total number of premature ventricular contractions (p less than 0.05) than dogs that underwent trauma alone. Following the first 10 minutes, ventricular irritability increased with time until approximately 1 hour, and then there was a gradual reduction of the frequency of arrhythmias in both dogs that received alcohol and those that did not. In conclusion, nonpenetrating cardiac impact in dogs that previously received ethanol was associated with greater ventricular irritability than in dogs that underwent impact alone.

High doses of prochlorperazine for cisplatin-induced emesis. A prospective, random, dose-response study.

This study investigated the antiemetic properties of four different doses of prochlorperazine (10 mg, 20 mg, 30 mg, 40 mg) when given randomly to patients receiving four cycles of the same dose of cisplatin-based chemotherapy. Prochlorperazine was given to 71 patients by slow intravenous infusion 30 minutes before and 3 and 6 hours after the start of cisplatin chemotherapy. The higher doses of prochlorperazine proved to be effective in the control of cisplatin-induced emesis. For the 20 patients who completed all 4 study cycles of treatment, a relationship was discerned between the dose of prochlorperazine administered and the antiemetic effect. When all 71 patients were analyzed in terms of the results of the first cycle of chemotherapy, a significant dose-response effect was also found. Overall toxic reactions in 82 treatment cycles using either 30 mg or 40 mg of prochlorperazine were dystonia (1 patient), restlessness (2), hypotension (3), and drowsiness (12). This study demonstrates that higher-than-conventional doses of prochlorperazine have an impressive antinauseant effect with only moderate toxicity.

Continuous hepatic artery infusion with an implantable pump: problems with hepatic artery anomalies.

The implantable pump for continuous hepatic artery chemotherapy requires even distribution of the chemotherapy to the whole liver for maximum efficacy. The hepatic arterial supply and its anomalies must be understood to achieve this. We reviewed the arteriograms of 100 patients who were potentially arterial perfusion candidates. Fifty percent had normal hepatic arterial anatomy. Twenty percent had a replaced or accessory right hepatic artery and 17% had an accessory or replaced left hepatic artery. The methods used to implant the pump catheters in these anomalous situations were reviewed. The use of dual catheter pumps for arterial anomalies has necessitated extended operative time and increased the risk of uneven hepatic perfusion. Catheterization of the portal vein, which is technically simpler, deserves consideration as an alternative in the presence of an aberrant arterial system.

Preoperative staging with computerized axial tomography and biochemical laboratory tests in patients with hepatic metastases.

Preoperative biochemical liver function tests and computerized axial tomographic (CAT) scans were performed on 100 patients as part of a prospective randomized study of treatments for liver metastases from colorectal cancer. The CAT scans reliably reflected the presence of disease in most patients but only accurately demonstrated the number and location of metastases in 43% of the patients. Extrahepatic metastases were present in 35 patients but were only seen on the CAT scans in three of these patients. The biochemical tests, which were useful for detecting hepatic metastases, were alkaline phosphatase (AP), lactic dehydrogenase (LDH), and carcinoembryonic antigen (CEA). When hepatic disease was minimal, these tests were less likely to be elevated than when there was extensive disease. Even with the combination of late generation CAT scans and biochemical tests, the accurate quantification and location of hepatic metastases and extrahepatic disease require a surgical assessment.

Sclerosing cholangitis after continuous hepatic artery infusion of FUDR.

Eight of 46 (17.4%) patients treated in our trial of continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) by Infusaid pump developed biliary strictures. The lesions were clinically, radiographically, and pathologically identical to the idiopathic sclerosing cholangitis frequently seen in association with inflammatory bowel disease. Treatment included immediate cessation of intraarterial FUDR, and surgical or percutaneous drainage of the biliary tree if it was dilated. Two of the eight patients died of the complication. Three patients stabilized after biliary system drainage, and two patients improved on observation only. The pathogenesis of this complication is not understood. This report details the clinical and pathological features of this entity.

Alterations of myoelectric activity associated with Campylobacter jejuni and its cell-free filtrate in the small intestine of rabbits.

We evaluated the effects of a culture of Campylobacter jejuni and its cell-free filtrate on myoelectric activity of isolated ileal segments in New Zealand White rabbits. Hematoxylin and eosin staining and scanning electron microscopy were used to assess the association between histologic changes and alterations in intestinal myoelectric activity. A culture of C. jejuni was shown to cause a significant increase in repetitive bursts of action potentials (RBAPs) (6.9 +/- 1.2 RBAP/h; p less than 0.001) compared with controls (0.3 +/- 0.1). Cell-free filtrates of C. jejuni cultures were also observed to induce RBAPs (5.0 +/- 0.9 RBAP/h; p less than 0.001). The fraction within the filtrate that induces alterations in motility was not destroyed by heating to 100 degrees C for 15 min (6.3 +/- 1.2 RBAP/h). Although no gross histologic changes were noted by hematoxylin and eosin staining of intestine exposed to a culture of C. jejuni for 8 h, blunting of villi with a cellular infiltrate was noted in rabbits exposed for 24 h. Scanning electron microscopy disclosed patchy villous tip damage in 3 of 5 animals exposed to cell-free filtrates for 8 h. These studies suggest C. jejuni is pathogenic and produces a heat-stable substance that alters intestinal myoelectric activity in rabbits.

Experience with continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. A prospective randomized study.

Sixty-five patients with hepatic metastases from colorectal primaries were studied in a prospective randomized fashion. The five patients with solitary metastases all had resection of metastases and 50% were randomized to pump therapy. Of the 16 patients with multiple resectable metastases, 7 had pump only and 9 had resection plus pump. Although the difference was not significant, there was a trend of improved survival for the patients with resection plus pump. For the patients with unresectable disease, those patients with positive portal nodes had poor survival matching those patients with extra hepatic metastases. Patients with unresectable disease treated with pump had a 73% therapeutic response rate and a median survival of 22 months. Significant complications included chemical hepatitis and biliary stenosis. The long-term efficacy of continuous hepatic artery infusion versus the hazards of treatment and the financial cost will need further investigation.