Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.     

Characteristics of Acute Asthma Patients Attended Frequently Compared with Those Attended Only Occasionally in an Emergency Department

Asthma patients that depend on emergency department (ED) services are generally considered to have extremely poor disease control and prognosis. It is important to identify characteristics related to poor disease control and frequent visits to the ED to apply appropriate clinical management. This study comprised a cross-sectional survey of consecutive patients with asthma exacerbation (age ≥12 years) presenting at the adult ED of a large, tertiary care, university-affiliated hospital over a 2-month period. The frequent visitors (FV) were defined by ≥3 visits to the ED in the preceding year, and the occasional visitors (OV) by ≤2 visits. Eighty-six patients (61 females and 25 males) were included in the study (mean age 38 ± 18 years). Of these patients, 51.2% were FV and 48.8% were OV. Sixty-nine percent had annual income lower than A$3000 and 66.3% had ≤8 years of the formal education. Only 18.6% had used inhaled corticosteroids, 79.1% identified the asthma attack severity, 70.9% increased or initiated inhaled β-agonist, 20.9% increased or initiated steroid therapy, and 55.8% had an asthma action plan for attack. The number of hospital admissions in past year (OR 4.3, P = .02), use of home nebulizer (OR 3.6, P = .05) and the lack of a written asthma action plan (OR 3.3, P = .03) were independently associated with frequent visits to the ED. We conclude that a substantial proportion of the patients that visit the ED are FV. These patients are more likely to have hospital admission in the past year, to use a home nebulizer, and to lack a written asthma action plan. They should be considered the most important target for asthma education.     

Parallel image reconstruction using B-spline approximation (PROBER).

A new reconstruction method for parallel MRI called PROBER is proposed. The method PROBER works in an image domain similar to methods based on Sensitivity Encoding (SENSE). However, unlike SENSE, which first estimates the spatial sensitivity maps, PROBER approximates the reconstruction coefficients directly by B-splines. Also, B-spline coefficients are estimated at once in order to minimize the reconstruction error instead of estimating the reconstruction in each pixel independently (as in SENSE). This makes the method robust to noise in reference images. No presmoothing of reference images is necessary. The number of estimated parameters is reduced, which speeds up the estimation process. PROBER was tested on simulated, phantom, and in vivo data. The results are compared with commercial implementations of the algorithms SENSE and GRAPPA (Generalized Autocalibrating Partially Parallel Acquisitions) in terms of elapsed time and reconstruction quality. The experiments showed that PROBER is faster than GRAPPA and SENSE for images wider than 150x150 pixels for comparable reconstruction quality. With more basis functions, PROBER outperforms both SENSE and GRAPPA in reconstruction quality at the cost of slightly increased computational time.     

Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial.

In a multicenter trial of adjuvant therapy in stage II breast cancer, 719 postmenopausal patients were randomized to one of three treatment regimens: radiotherapy only or in combination with adjuvant tamoxifen for one year, or adjuvant tamoxifen without radiotherapy. At twelve years of follow-up (median 9 years), no statistically significant differences in survival or recurrence-free survival were observed. However, the rate of loco-regional recurrency was lower among patients treated with both radiotherapy and tamoxifen. The rate of bilateral breast cancer was reduced in tamoxifen-treated patients whereas the rate of new primary malignancies other than breast cancer was somewhat higher in tamoxifen-treated patients. Adjuvant therapy in breast cancer may influence not only breast cancer recurrences and mortality but also later disease patterns and cause-specific mortality.     

Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data. Received: 23 September 1998 / Accepted: 28 September 1998     

Biomonitoring of benzene exposure by trace analyses of phenylguanine

Summary From preliminary experiments it was known that radiolabelled benzene and some of its metabolites during its metabolic activation process produce different in vitro DNA-phenyladducts in mitoplasts [5, 11].As we reported previously [9] at least one of these adducts, N-7-phenylguanine, is excreted in the urine of rats in measurable amounts, probably through an excision-repair mechanism after an inhalation experiment. Now we found, after i.p. application of benzene in the urine of rats, a compound separated by cation-exchange chromatography that behaves like a synthezised N-7-phenylguanine reference substance with respect to its retention index and the UV-absorption. This finding could be confirmed by HPLC-measurements with reversed-phase carrier materials. Silylation and gaschromatographic/mass spectrometric (GC/MS) separation of the fraction, which contains the phenylguanine, revealed that these fractions contain further phenyl adducts. Furthermore we studied the time-dependent excretion of the DNA-base adduct. Surprisingly the excretion dropped to zero on the fourth day and showed a new increase thereafter.     

Organ culture of pig cornea: biochemical analyses of mid-term-stored corneal tissue

Freshly prepared pig corneas were cultured at 22 degrees C in TC 199 medium supplemented with HEPES buffer, antibiotics and 10% sterile pig blood serum. The cultures were maintained in a closed system up to 30 days. The hydration as measured by wet and dry weights increased from 80 to 94% after 2 weeks of storage. Glucose decreased slowly and continuously during the culture time by 0.32 mmol in 30 days. This was equivalent to 11 mumol/day, 0.46 mumol/h and finally 0.264 mumol/h/cm2. Lactate increased in the culture accordingly by 0.34 mumol/h/cm2. In the corneal epithelium of the cultured tissues the glucose levels--normally at about 5 mumol/g--equilibrated with those of the medium during the first 10 days; later the epithelial glucose levels increased up to 20-30 mumol/g. The glycogen content of the epithelium remained constant for the first 10 days of storage. The ATP/ADP ratios in the corneal epithelium initially decreased but later recovered to values of about 12. The pO2 in the culture system decreased from 156 to 120 mm Hg, which is equivalent to an oxygen consumption of 7.41 microliters O2/h/cm2. The CO2 production initiating from a level of 16.6 mm Hg was 4.88 microliters/h/cm2. The data showed that the cornea was viable in this culture system for 30 days.     

Healthcare workers' risk of contact with body fluids in a hospital: the effect of complying with the universal precautions policy.

OBJECTIVE: To test whether healthcare workers' knowledge of and compliance with the basic principle of the Universal Precautions policy (i.e., that all patients should be treated equally regarding contact with body fluids) influenced the rate of contact with patient blood. DESIGN: Survey based on anonymous questionnaires. SETTING: A 380-bed secondary and tertiary care hospital receiving emergency and elective patients. PARTICIPANTS: All employees having any contact with patients. Nine hundred one of 1,308 (69%) of the questionnaires were returned. RESULTS: Twelve percent of the respondents (95% confidence interval [CI95] = 10.0%-14.4%) had experienced any contact with patient blood in the week preceding their answer. Physicians had the highest rate of contact with blood followed by nurses. In the five groups--physicians, nurses, laboratory technicians and phlebotomists, nursing aides, and student nurses--contact with blood was less frequent in the subgroup that did know and comply with the basic principle of the Universal Precautions policy, compared with the subgroup that did not. When adding the results for the 5 groups, contact with blood was experienced by 91 of 571 (15.9%, CI95 = 13%-19%) of the personnel who did not know and comply with Universal Precautions. The personnel who did know and comply with Universal Precautions had a significantly lower (9 of 111 [8.1%], p < .05, CI95 = 3.8%-15%) rate of contact with blood. CONCLUSIONS: The healthcare workers who knew and complied with Universal Precautions had a significant lower rate of contact with patient blood than those who did not.