Termination of pregnancy at 9-13 weeks' amenorrhoea with mifepristone and misoprostol

The effectiveness of a combined regimen of mifepristone and vaginal misoprostol for termination of pregnancies of 9-13 weeks of gestation was investigated in 120 UK abortion patients (median age, 22.1 years; median duration of amenorrhea, 10.3 weeks). Each woman received a single oral dose of 200 mg of mifepristone 36-48 hours before admission, at which time 800 mcg of misoprostol was administered vaginally. Where indicated, a further two doses of 400 mcg of misoprostol (vaginal or oral) were provided every 3 hours. All 120 women aborted on the day of prostaglandin administration; however, 6 women (5%) required exploratory curettage after the procedure for retained placenta. The median prostaglandin dose was 1200 mcg (range, 800-1600 mcg). The median time from misoprostol administration to abortion was 4.33 hours (range, 1.3-16.0 hours). 60 women (50%) required oral analgesics and 26 (22%) received parenteral analgesia. Diarrhea occurred in 38 women (32%). The median duration of bleeding after abortion was 12.5 days (range, 3-43 days). In questionnaires administered to 73 women, only 3 (4%) expressed dissatisfaction with medical abortion, because of pain or prolonged bleeding. The relatively high dose of misoprostol used in this study and the vaginal route of administration are presumed to account for the 95% success rate. Extension of medical abortion to later gestation times would decrease the need for surgery and expand women's choice of methods of pregnancy termination.     

A study of self poisoning with oral salbutamol--laboratory and clinical features

A review of 35 patients > 60 years of age with odontoid fractures showed that a type II injury (Anderson and D'Alonso) was the most common fracture pattern (82% of cases). On the basis of mechanism of injury and sex incidence, we deduced that osteopenia is a contributory factor in the occurrence of odontoid fractures. A fall in a domestic setting was the cause in 53%. The peg was posteriorly displaced in 88% of type II fractures, and primary union occurred in 23%. The incidence of concomitant spinal cord injury with type II fractures was higher in older patients than it was in those < 60 years of age. The outcome for these patients was largely determined by their neurological status at presentation. Myelopathy as a late complication of nonunion was not observed in nine patients with an average follow-up of 21 months. The data suggest that vigorous attempts to secure both primary union and a sound arthrodesis for non-union are questionable in the elderly except in unusual circumstances.     

Gene amplification in a p53-deficient cell line requires cell cycle progression under conditions that generate DNA breakage

Amplification of genes involved in signal transduction and cell cycle control occurs in a significant fraction of human cancers. Loss of p53 function has been proposed to enable cells with gene amplification to arise spontaneously during growth in vitro. However, this conclusion derives from studies employing the UMP synthesis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to selecting for cells containing extra copies of the CAD locus, enables p53-deficient cells to enter S phase and acquire the DNA breaks that initiate the amplification process. Thus, it has not been possible to determine if gene amplification occurs spontaneously or results from the inductive effects of the selective agent. The studies reported here assess whether p53 deficiency leads to spontaneous genetic instability by comparing cell cycle responses and amplification frequencies of the human fibrosarcoma cell line HT1080 when treated with PALA or with methotrexate, an antifolate that, under the conditions used, should not generate DNA breaks. p53-deficient HT1080 cells generated PALA-resistant variants containing amplified CAD genes at a frequency of >10(-5). By contrast, methotrexate selection did not result in resistant cells at a detectable frequency (<10(-9)). However, growth of HT1080 cells under conditions that induced DNA breakage prior to selection generated methotrexate-resistant clones containing amplified dihydrofolate reductase sequences at a high frequency. These data demonstrate that, under standard growth conditions, p53 loss is not sufficient to enable cells to produce the DNA breaks that initiate amplification. We propose that p53-deficient cells must proceed through S phase under conditions that induce DNA breakage for genetic instability to occur.     

Hydrogen limitation--a method for controlling the performance of membrane biofilm reactor for autotrophic denitrification of wastewater.

Hydrogen-driven denitrification using the fiber membrane biofilm reactor (MBfR) was evaluated for consistent operation in tertiary wastewater treatment. The possibility of controlling the process rates, as well as biofilm parameters by supplying limited amounts of electron donor (hydrogen), was tested. Limiting the hydrogen supply proved to be efficient in controlling the biofilm growth and performance of the MBfR. Denitrification rates remained unchanged for both synthetic wastewater (SWW) and real municipal wastewater (MWW) effluent as well through the fluctuations in the substrate (NO3-N) concentration. The average denitrification rates were 0.50 (+/- 0.02) g NO3-N per day per m2 for SWW and 0.59 (+/- 0.04) g NO3-N per day per m2 for MWW. Biofilm density rather than thickness was the determining factor in substrate diffusion and biofilm sloughing, ultimately determining operating stability. Limited hydrogen supply assured constant volatile solids (VS) concentration in the biofilm. It was determined that VS/TS ratio higher than 0.25 assured stable biofilm operation. Decrease of VS/TS ratio below 0.25 led to shearing of the nonbiological outer layers of the biofilm. The values of chemical oxygen demand (COD), volatile suspended solids (VSS) and total suspended solids (TSS) in the final effluent were stable and well below wastewater effluent guidelines. Substitutions of bicarbonate with gaseous carbon dioxide as the carbon source did not affect denitrification rates despite lower than optimum pH conditions.     

Urinary excretion of apo(a) fragments in NIDDM patients

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.     

Education for the nurse of tomorrow: a community-focused curriculum

A competitive enzyme-linked immunoadsorbent assay (ELISA) technique has been developed to facilitate quantitative analysis of the earliest step in the initiation of the extrinsic pathway of coagulation, i.e., complex formation of factor VII/VIIa with tissue factor. The ELISA measures the binding of biotinylated human plasma factor VII to relipidated recombinant human tissue factor. Quantitation of the relative affinity (expressed as IC50) of any factor VII molecular population or structural analogue for tissue factor can be determined by competitive binding. Subnanomolar concentrations of both wild-type recombinant human factor VII (rFVII) and rFVII(R152Q), a mutation at the FVII activation site, competed effectively with biotinylated plasma-derived factor VII in binding to tissue factor. In contrast, the affinity of rFVII(R79Q), a mutation in the first epidermal growth factor-like domain, was 12-fold lower. Following activation of rFVII(R79Q), its affinity for tissue factor and enzymatic activity increased 4-fold and 6-fold, respectively. For wild-type rFVII, enzymatic activity rose significantly following activation. However, its affinity for tissue factor was unchanged. We conclude that both the activation state of factor VII and the mutation of amino-acid residues within the first epidermal growth factor-like domain may alter the affinity of factor VII for tissue factor.     

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.