A comparison of high vs standard tidal volumes in ventilator weaning for individuals with sub-acute spinal cord injuries: a site-specific randomized clinical trial.

STUDY DESIGN: Prospective, randomized, controlled parallel group trial with single-blinded data analysis. OBJECTIVES: To determine the safety and efficacy of higher (20 ml kg(-1) ideal body weight (IBW)) vs standard (10 ml kg(-1) IBW) tidal volumes (Vt) for patients with sub-acute traumatic tetraplegia during ventilator weaning using a 14-day (minimum) weaning protocol. SETTING: United States regional spinal cord injury treatment center. METHODS: Thirty-three ventilator requiring inpatients were randomized to either the higher (Group 1) or the standard (Group 2) Vt protocol. Initially, all patients were ventilated at 10 ml kg(-1) IBW Vt and 5 cm H(2)O [corrected] of PEEP for 72 h. For Group 1, Vt was raised 100 ml kg(-1) until reaching target Vt of 20 ml kg(-1) IBW. Group 2 was maintained at Vt of 10 ml kg(-1) IBW. Plateau pressures were kept at or below 30 cm H(2)O. [corrected]. Safety outcomes included incidence of adverse events. RESULTS: Because of smaller than expected enrollment, evaluation of efficacy was not possible. Therefore, we report the safety outcomes of 33 study participants. The 16 patients in Group 1 and 17 patients in Group 2 were demographically similar at baseline, except for age. The average age was 39.3 years in Group 1 and 27.2 years in Group 2, (P=0.002). There was no difference in median days to wean: 14.5 days in Group 1 and 14 days in Group 2. The incidence of adverse pulmonary events was similar between groups. CONCLUSION: Higher tidal volumes can be safely utilized during weaning of patients with tetraplegia from mechanical ventilation using a 14-day weaning protocol.

Medicines can affect thermoregulation and accentuate the risk of dehydration and heat-related illness during hot weather.

WHAT IS KNOWN AND OBJECTIVE: Hot days are increasingly common and are often associated with increased morbidity and mortality, especially in the elderly. Most heat-related illness and heat-related deaths are preventable. COMMENT: Medicines may accentuate the risk of dehydration and heat-related illness, especially in elderly people taking multiple medicines, through the following mechanisms: diuresis and electrolyte imbalance, sedation and cognitive impairment, changed thermoregulation, reduced thirst recognition, reduced sweat production, and hypotension and reduced cardiac output. WHAT IS NEW AND CONCLUSION: Commonly used medicines that may significantly increase the risk include diuretics, especially when combined with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), anticholinergics and psychotropics. Initiation of individualized preventive measures prior to the start of the hot weather season, which includes a review of the patient and their medicines to identify thermoregulatory issues, may reduce the risk of heat-related illness or death.

Antecedents of eating disorders and muscle dysmorphia in a non-clinical sample.

Muscle Dysmorphia (MD) has recently been conceptualized as the male form of Eating Disorders (ED); although, it is not currently classified as an ED. The current study compares etiological models of MD symptomatology and ED symptomatology. It was hypothesized that sociocultural influences on appearance (SIA) would predict body dissatisfaction (BD), and that this relationship would be mediated by self-esteem (SE) and perfectionism (P); that BD would predict negative affect (NA); and that NA would predict MD and ED symptomatology. Two-hundred-forty-seven female and 101 male college students at a midsouth university completed the study. All participants completed measures assessing each of the constructs, and multiple regression analyses were conducted to test each model's fit. In both models, most predictor paths were significant. These results suggest similarity in symptomatology and etiological models between ED and MD.

Stability indicating HPLC method for the estimation of oxycodone and lidocaine in rectal gel.

An HPLC method for the quantification of oxycodone and lidocaine in a gel matrix is described. The mobile phase consisted of methanol--water--acetic acid (35:15:1 v/v/v) and was delivered at 1.5 ml/min through a 4.6 x 250 mm Zorbax SB-C8 column. Oxycodone was detected at 285 nm and lidocaine at 264 nm. Linear calibration curves were obtained for oxycodone in the range of 0.05--1.5% (w/w) and for lidocaine in the range of 0.1--5.0% (w/w). Oxycodone and lidocaine were treated with hydrogen peroxide and the oxidation products were readily separated on the column. The method was applied to assess the stability of a gel containing oxycodone hydrochloride (0.3% w/w) and lidocaine (1.5% w/w). The gel was stored under refrigeration in ready-to-use syringes and under these conditions oxycodone and lidocaine were stable for at least 1 year. The gel is useful in the management of tenesmus in rectal cancer.

Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma.

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.

Rituximab: the first monoclonal antibody approved for the treatment of lymphoma.

Rituximab, a genetically engineered monoclonal chimeric antibody, targets the CD20 antigen expressed on B cells. It was approved by the US Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma (LG/F NHL), and by the European Agency for the Evaluation of Medicinal Products on June 2, 1998, for therapy of patients with Stage III/IV, follicular, chemoresistant or relapsed NHL. Eight Phase II or II clinical trials in LG/F NHL patients have been completed: five single-agent studies and three combination studies. Rituximab has a favorable safety profile: most adverse events (AEs) are Grade 1 or 2, and the frequency of AEs decrease with subsequent infusions. AEs in the combination studies are consistent with those seen with individual agents. For evaluable patients in the single-agent studies, overall response rates (ORR) ranged from 40% to 60%, median duration of response (DR) ranged from 5.9 to 15.0+ months, and median time to progression (TTP) ranged from 8.1 to 19.4+ months. For evaluable patients in the combination studies, the ORR ranged from 45% to 100%, median DR ranged from 11.7+ to 39.1+ months, and median TTP ranged from 12.9+ to 40.5+ months. Studies in intermediate- and high-grade NHL are ongoing. Long-term development plans include evaluating the safety and efficacy of rituximab in various types of lymphoma and in combination with other lymphoma regimens. Future studies may explore ways to increase rituximab efficacy by upregulating CD20 or increasing effector function with different cytokines.

Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.

Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. It also has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis. It was approved by the Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma Rituximab is the first monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy of a lymphoma. The recommended dose is rituximab 375 mg/m2 intravenously weekly x4 infusions. Treatment is well tolerated and outpatient therapy is feasible. Adverse events are mostly grades I and 2, occurring primarily with the first infusion. In a phase II single-agent clinical trial, the overall response rate was 50%, with a median time to progression in responders of 10.2 months. In a larger multicenter trial involving 166 patients, the overall response rate was 48% with 6% complete and 42% partial responses. Median time to progression for responders was 13.2 months and median duration of response was 11.6 months. A 40% response rate has been observed on re-treatment with rituximab. Activity also has been seen in patients with bulky disease. Combination studies have been performed with interferon, cyclophosphamide/doxorubicin/vincristine/prednisone, and radioimmunotherapy. Rituximab, the first monoclonal antibody approved for the treatment of cancer, is safe and effective in treating patients with relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma.

Continuous subcutaneous heparin infusion for treatment of Trousseau's syndrome.

OBJECTIVE: To describe the use of continuous subcutaneous heparin infusion in the treatment of 2 cases of Trousseau's syndrome. CASE SUMMARIES: Two patients with metastatic carcinoma presented to the hospital with acute coagulopathies consistent with a diagnosis of Trousseau's syndrome. In both cases conventional anticoagulant therapies proved to be impractical and ineffective. DISCUSSION: Considerable literature suggests that oral anticoagulants such as warfarin are ineffective in the treatment of Trousseau's syndrome. Heparin is more effective for this purpose, although continuous intravenous infusion may prove difficult in the ambulatory setting. Intermittent subcutaneous injections of heparin or low-molecular-weight heparin may not provide reliable anticoagulation for the entire dosage interval. Although the use of continuous subcutaneous infusion of heparin has been used for anticoagulation during pregnancy, this is the first report of the use of sodium heparin administered by continuous subcutaneous infusion in the treatment of Trousseau's syndrome. CONCLUSIONS: Continuous subcutaneous heparin infusion may be an effective option for the treatment of Trousseau's syndrome in the ambulatory setting.

Effect of Re-17 mutant Salmonella typhimurium bacterin toxoid on clinical coliform mastitis.

The objective of this study was to test the hypothesis that the incidence and severity of clinical coliform mastitis could be decreased by Re-17 mutant Salmonella typhimurium bacterin toxoid. Holstein-Friesian cows from two Arizona dairies were selected for this study based on July through November projected calving dates; peak lactation occurred during the period of highest rainfall and peak environmental stress. The cows were randomly assigned to either a vaccinate or a control group, and 1292 cows were paired by herd, parity, calving date, and milk yield. The 646 vaccinates were injected twice during the third trimester of pregnancy with an Re-17 mutant S. typhimurium bacterin toxoid, and the 646 controls were not vaccinated. Vaccinated cows had significantly fewer clinical cases of coliform mastitis with positive coliform cultures and had lower culling rate from coliform mastitis than control cows during the first 5 mo of lactation. During the same period, the mortality rate from clinical coliform mastitis was 75% less in the vaccinated clinical coliform mastitic group than in the control group. Incidence of mastitis increased with advancing parity. The Re-17 mutant Salmonella typhimurium bacterin toxoid provided cross-protection against coliform mastitis; incidence and severity of clinical coliform mastitis were significantly lowered during the first 5 mo of lactation.

Revoking hospital privileges: new directions in Ontario. Dr. N. v. Brantford General Hospital.

Recent decisions by the Ontario Hospital Appeal Board have helped hospital boards understand the importance of due process when revoking a physician's hospital privileges. The authors illustrate the need to have a mechanism to suspend privileges immediately but which also provides physicians with the opportunity to respond to allegations. The article outlines 11 clauses that serve as a practical guide to due process and can be added to hospital by-laws.

A conflict of interest policy for hospitals.

As the environment in which community hospitals operate becomes ever more complex, the opportunity for conflict of interest between the hospital and members of its governing board increases. This article examines the duties and responsibilities of hospital trustees and the ways in which hospitals can identify and manage conflict of interest.

The HEMOPUMP cardiac assist system: nursing care of the patient.

This article uses a case study to demonstrate the support provided by the HEMOPUMP temporary cardiac assist system. The Nursing Plan of Care addresses the actual and potential problems encountered by the critical care nurse.

Local compression patterns beneath pneumatic tourniquets applied to arms and thighs of human cadavera.

Distributions of tissue fluid pressure were examined beneath a standard pneumatic tourniquet in six upper extremities and six lower extremities of fresh human cadavera, disarticulated at the shoulder and hip, respectively. A standard 8-cm-wide tourniquet cuff was applied at mid-humerus or mid-femur position. Tissue fluid pressures were measured by 100-cm-long slit catheters inserted parallel to the bone at four tissue depths: subcutaneous, subfascial, mid-muscle, and adjacent to bone. All arms and thighs were studied at the following cuff pressures: 100, 150, 200, 250, 300, 400, and 500 mm Hg. Tissue fluid pressure was always maximal in subcutaneous tissue at mid-cuff. Transmission of cuff pressures to deeper tissues was significantly less (p less than 0.01) in the thighs with a girth of 40-52 cm than in the arms with a girth of 22-33 cm. At the four tissue depths studied, tissue fluid pressures fell steeply in a longitudinal direction near the cuff edge to levels near zero at points 1-2 cm outside each cuff edge. Our results suggest that wider cuffs are required on thighs than on arms to provide a bloodless field during limb surgery and to minimize underlying tissue injury associated with high cuff pressures. Our recommendation for wider tourniquet cuffs than those presently used during orthopaedic surgery is contrary to recent prevailing knowledge.