A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise.

BACKGROUND: Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia. METHODS: Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores. RESULTS: Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2. CONCLUSIONS: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension.

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

BACKGROUND: The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. METHODS: Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. RESULTS: Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. CONCLUSIONS: Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam.

OBJECTIVE: To report a patient with a probable acute tubular necrosis (ATN) induced by chronic exposure to polyethylene glycol (PEG)-400 via long-term, massive dosage of intravenous lorazepam. CASE SUMMARY: A 57-year-old man with a history of alcohol abuse was admitted to the intensive care unit for acute respiratory failure. Lorazepam therapy was initiated in anticipation of alcohol withdrawal. Dosages up to 18 mg/h were required to provide adequate sedation and optimize ventilation. On day 43, the patient developed oliguric ATN of unknown etiology. The cumulative intravenous lorazepam dose was 4089 mg, equivalent to approximately 220 mL of PEG-400. Blood urea nitrogen concentrations followed a pattern that paralleled lorazepam dosage increases and decreases. Protein and granular casts were evident in urinalyses performed on days 12 and 29. The patient eventually experienced complete recovery. DISCUSSION: ATN associated with intravenous PEG was last reported in 1959 in 6 of 32 patients receiving a cumulative PEG-300 dose of 120-200 mL over 3-5 days via an intravenous nitrofurantoin preparation. Two of the 6 patients died. Chronic administration of intravenous PEG to rabbits over a 5-week period has caused cloudy swelling of the renal tubular epithelium, increased blood urea concentrations, and death in some animals. CONCLUSIONS: ATN probably resulted from chronic PEG exposure via massive doses of lorazepam injection, possibly enhanced by concurrent administration of vancomycin.

Glycosylation and antigenic variation among Kunjin virus isolates.

Previous studies have found Kunjin (KUN) virus isolates from within Australia to be genetically homogenous and that the envelope protein of the type strain (MRM61C) was unglycosylated and lacked a potential glycosylation site. We investigated the extent of antigenic variation between KUN virus isolates from Australia and Sarawak using an immunoperoxidase assay and a panel of six monoclonal antibodies. The glycosylation status of the E protein of each virus was also determined by N glycosidase F (PNGase F) digestion and limited sequence analysis. The results showed that KUN viruses isolated within Australia oscillated between three antigenic types defined by two epitopes whose expression was influenced by passage history and host cell type. In contrast an isolate from Sarawak formed a stable antigenic type that was not influenced by passage history and was distinct from all Australian isolates. PNGase F digestions of KUN isolates indicated that 19 of the 33 viruses possessed a glycosylated E protein. Nucleotide sequence of the 5' third of the E gene of selected KUN isolates revealed that a single base change in PNGase F sensitive strains changed the tripeptide N-Y-F (amino acids 154-156 of the published sequence) to the potential glycosylation site N-Y-S. Further analysis revealed that passage history also had a significant influence on glycosylation.

Degradation and inactivation of antitumor drugs.

Chemical methods for the degradation of 11 antineoplastic drugs [etoposide, teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy-bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine, lomustine, and methotrexate] were investigated. The success of the degradation procedures was assessed by HPLC and degree of biological inactivation by mutagenicity assays. The most widely applicable procedure was oxidation with potassium permanganate or 5.25% sodium hypochlorite solution (bleach). Oxidation completely degraded and inactivated etoposide, teniposide, bleomycin, mitomycin C, and methotrexate. In addition, oxidation followed by nucleophilic substitution resulted in the complete degradation and inactivation of cyclophosphamide and ifosfamide. Although carmustine and lomustine were chemically degraded by treatment with acidic potassium permanganate, the resulting reaction mixtures remained mutagenic. Therefore, this procedure cannot be recommended. The platinum-containing compounds, cisplatin and CHIP, were rendered nonmutagenic by reaction with sodium diethyldithiocarbamate. These easily performed, relatively safe procedures can be used to prevent exposure to mutagenic wastes and spills in the hospital setting.

Treatment of chemical and biological warfare injuries: insights derived from the 1984 Iraqi attack on Majnoon Island.

The potential use of chemical and biological weapons, while being banned by international treaties, has never been higher than now. The current Persian Gulf crisis, and the easy availability of these weapons by "terrorist nations," makes the danger all too real. The experience derived from the Iraqi attack on Majnoon Island demonstrates the devastating effects of these weapons when used during modern warfare. Exposure to the agents used during the 8 years of the Iran-Iraq War results in a triad of injuries: skin burns, ocular damage, and pulmonary distress. Specific antidotes are available for some agents used in warfare; however, the clinical presentation following exposure to the different toxins is extremely similar, making a bedside diagnosis of the specific agent involved almost impossible. The Majnoon Island experience has shown the value of prevention, when possible, and decontamination, of both casualties and equipment. The prompt implementation of general treatment strategies, as well as specific antidotes, are paramount for the successful management of patients after a chemical weapons attack.

Refractive-index measurements of the beta'' aluminas.

The refractive indices of selected monovalent and divalent beta'' alumina single crystals are determined using prism refraction techniques. The birefringence is found to vary from uniaxial negative to uniaxial positive depending on the electronic polarizability of the exchanged ion. Thus, beta'' alumina is a novel material in which the magnitude and polarity of the birefringence can be tuned simply by ion exchange. The refractive-index data are used to predict an isoindex point (n(e) = n(0)) for the mixed-system Na(+)-Ag(+) beta'' alumina compositions.

Stability of dicloxacillin sodium oral suspension stored in polypropylene syringes.

The stability of dicloxacillin sodium in oral suspension stored in clear polypropylene oral syringes was studied. Commercially available dicloxacillin sodium powder for oral suspension from a single lot was reconstituted according to the manufacturer's instructions and drawn into 5-mL clear polypropylene oral syringes. The syringes were divided into groups and stored at -20, 4, 25, 40, 60 or 80 degrees C. Two additional lots were similarly reconstituted, repackaged, and stored at 80 degrees C only to assess interlot variability. Powder in the original containers was similarly reconstituted according to the manufacturer's instructions, and the containers were divided into groups and stored with the syringes. Immediately after reconstitution and at specified times during storage, three syringes and the original containers at each storage temperature were removed, and their contents were analyzed for dicloxacillin sodium concentration using the Standard USP Iodometric Assay. Dicloxacillin sodium follows a first-order rate of degradation at temperatures of 40, 60, and 80 degrees C. The rate of degradation changes to a zero-order process at temperatures of 25, 4, and -20 degrees C. At all temperatures, degradation occurred more rapidly when the drug was repackaged into unit dose polypropylene oral syringes than in the manufacturer's original container. Dicloxacillin sodium reconstituted from powder as oral suspension and repackaged in clear polypropylene syringes was stable for no longer than 7, 10, and 21 days when stored under ambient, refrigerated, and frozen conditions, respectively.

Toxicity, immunosuppressive effects and carcinogenic potential of volatile nitrites: possible relationship to Kaposi's sarcoma.

Volatile nitrite in the form of amyl nitrite was used for 100 years for the treatment of angina pectoris. In spite of recognized toxicity, its use in this form was considered safe. During the 1960s prescriptions were not required for purchase of amyl nitrite (called poppers) and its use for recreational purposes became popular. With reinstatement of the prescription requirement in 1969, non-medicinal, street-variety volatile nitrites were made commercially available in the form of mixtures of impure butyl and isobutyl nitrite; some of these preparations also included amyl nitrite. These products have been found to be profoundly immunosuppressive for human lymphocytes in vitro, and their by-products when metabolized into N-nitroso compounds have been known to be highly carcinogenic in many animal species. Recreational use of inhaled volatile nitrites is prevalent among male homosexuals and the compounds have been suspected as possible cofactors in Kaposi's sarcoma associated with the Acquired Immune Deficiency Syndrome (AIDS). This association could be explained by nitrite-induced vasodilation of rectal mucosal vessels providing a port of entry for a transmissible agent, by direct immunosuppression of the host allowing expression of a potentially oncogenic virus by co-carcinogenic effects of by-products by themselves or in conjunction with other putative cofactors such as cytomegalovirus. Nitrites should continue to be considered as a possible cofactor in the etiology of Kaposi's Sarcoma among male homosexuals and possibly those with other manifestations of AIDS.

Acquired immune deficiency syndrome and the management of associated opportunistic infections.

Since the spring of 1981, more than 2300 cases of acquired immune deficiency syndrome (AIDS) have been reported from 41 states to the Centers for Disease Control. Cases also have been reported from 20 foreign countries, and reports are increasing at an alarming rate. More than 900 people (approximately 40 percent) have died of this disease. AIDS is characterized by skin test anergy to recall antigens, decreased T-helper subset, and inverted helper T-cell:suppressor T-cell ratios in the peripheral blood. Overt AIDS may be preceded by a prodrome that may last for many months and consists of fever, weight loss, and lymphadenopathy. The immune defect in AIDS permits the development of opportunistic infections caused by a number of organisms, including Pneumocystis carinii, Mycobacterium avium-intracellulare, Toxoplasma gondii, and various fungi. Certain malignancies also are associated with AIDS, in particular, Kaposi's sarcoma. Although the etiology of AIDS is unknown, the causative agent appears to be infectious. Lifestyle factors such as drug use and certain sexual activities may play a role. Currently, epidemiologists and others investigating the syndrome believe that AIDS can spread through sexual contact, blood products, or both. AIDS patients include homosexual males, users of intravenous drugs, immigrants from Haiti, hemophiliacs, female partners of males with AIDS, infants born to mothers who have AIDS, and persons who have received blood products from AIDS patients. Thus far, questions about AIDS outnumber the answers. Intensive research is being conducted to develop a rational approach to the treatment of AIDS and a better understanding of the relationship between the immune defense system and cancer.