Elimination of antibiotic-resistant plasmids by quinolone antibiotics

Of 7 plasmids we tested, the plasmid pORF2 was eliminated in vitro with the most efficiency by treatment with subinhibitory concentrations of novobiocin, coumermycin and 10 quinolones. It showed a cure rate of 43% by enoxacin; 12% by novobiocin, pefloxacin, ciprofloxacin and CI-934; 7% by coumermycin and ofloxacin; 9% by amifloxacin; and 4% by AM-833. On the other hand, pSC194, pBR322 and pMH612 were poorly cured in vitro by quinolones, except pSC194 which was cured 33% by enoxacin. R1, pP1603, and pUB110 were unaffected by the treatment. Mice were challenged intraperitoneally with a 2XLD50 of Escherichia coli carrying the ORF2 plasmid and were treated per os with 1 X or 1/2 X ED50 of either enoxacin or CI-934. The frequency of loss of ampicillin resistance determined 3 h after treatment shows curing effects of 92% for CI-934, 89% for enoxacin and 20% for untreated control.     

The combination of prazosin and verapamil in the treatment of essential hypertension

An exaggerated fall in blood pressure has been reported with the combination of an alpha 1-blocker and a calcium antagonist. This study investigated, in a placebo-controlled, randomized crossover trial, the clinical usefulness of the combination of prazosin (2 mg b.i.d.) and verapamil (160 mg b.i.d.). Therapeutic efficacy was monitored at regular outpatient visits: average supine and erect blood pressures were, respectively, 175/99 and 176/103 mm Hg with placebo, 160/91 and 164/96 mm Hg with single drug treatment, and 152/84 and 152/89 mm Hg with combination therapy. This significant and clinically useful reduction in blood pressure had an overall magnitude of approximately 28/18 mm Hg (supine) and 29/19 mm Hg (erect). Further measurements were made during a series of intensive study days, and the most important additional finding was a pharmacokinetic interaction that resulted in increased peak concentrations and bioavailability of prazosin. In conclusion, the combination of prazosin and verapamil proved effective in the treatment of 12 patients with essential hypertension who had been poorly responsive to conventional treatment with a beta-blocker and thiazide diuretic.     

Discovery of methoxyacetylcarbamide in the urine of normal adults and phenylketonuric children

In order to study metabolic distinctions in phenylketonuria, urinary metabolites in the form of trimethylsilyl derivatives have been characterized by high resolution gas chromatography and mass spectrometry. A previously unknown metabolite has been found in the urine of some untreated phenylketonuric infants between 2 and 5 yr of age. The metabolite was absent in healthy children of the same age. The metabolite appeared to be present in the urine of apparently healthy adults (25-32 yr old). The metabolite was identified as methoxyacetylcarbamide on the basis of mass fragmentation analysis and compared with synthetic methoxyacetylcarbamide. Their retention times and mass spectra coincided.     

An analysis for blood manganese used to assess environmental exposure

In this graphite-furnace atomic-absorption spectrometric method for measuring manganese in whole blood, we use a pyrolytic platform to minimize interference by sample matrix. For optimal sample ashing we denature the sample within the furnace with nitric acid and use oxygen as the purge gas at low temperatures. The mean manganese concentration found in blood from 15 unexposed city dwellers was 215 (2 SD 135) nmol/L. By comparison, the range of manganese concentrations in blood sampled from a group of Australian aborigines living near a surface manganese ore deposit on Groote Eylandt, Northern Territory, was much higher (median 405 nmol/L, range 175 to 990 nmol/L).     

A Comparison Between Recipients Receiving Matched Kidney and Those Receiving Mismatched Kidney from the Same Cadaver Donor

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.     

Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism.

The theory of bifurcating vascular systems predicts vessel diameters that are related to optimality criteria like minimization of pumping energy or of building material. However, mechanisms for producing the postulated optimality have not been described so far, and quantitative data on bifurcation diameters during development are scarce. We used an embryonic vascular bed that rapidly grows and adapts to changing hemodynamic conditions, the chicken chorioallantoic membrane (CAM), and correlated vascular cast and tissue section morphology with in vivo time-lapse video monitoring. The bifurcation exponent delta and associated parameters were quantitatively assessed in arterial and venous microvessels ranging in diameter from 30 to 100 microm. We observed emergence of optimality by means of intussusception, i.e., formation of transvascular tissue pillars. In addition to intussusceptive microvascular growth (IMG = expansion of capillary networks) and intussusceptive arborization (IAR = formation of feeding vessels from capillaries) the observed intussusception at bifurcations represents a third variant of nonsprouting angiogenesis. We call it intussusceptive branching remodeling (IBR). IBR occurred in vessels of considerable diameter by means of two alternative mechanisms: either through pillars arising close to a bifurcation, which increased in girth until they merged with the connective tissue in the bifurcation angle; or through pillars arising at some distance from the bifurcation point, which then expanded by formation of ingrowing tissue folds until they became connected to the tissue of the bifurcation angle. Morphologic evidence suggests that IBR is a wide-spread phenomenon, taking place also in lung, intestinal, kidney, eye, etc., vasculature. Irrespective of the mode followed, IBR led to a branching pattern close to the predicted optimum, delta = 3.0. Significant differences were observed between delta at arterial bifurcations (2.70 to 2.90) and delta at venous bifurcations (2.93 to 3.75). IBR, by means of eccentric pillar formation and fusion, was also involved in vascular pruning. Experimental changes in CAM hemodynamics (by locally increasing blood flow) induced onset of IBR within less than 1 hr. Our study provides morphologic and quantitative evidence that a similar cellular machinery is used for all three variants of vascular intussusception, IMG, IAR, and IBR. It thus provides a mechanism of efficiently generating complex blood transport systems from limited genetic information. Differential quantitative outcome of IBR in arteries and veins, and the experimental induction of IBR strongly suggest that hemodynamic factors can instruct embryonic vascular remodeling toward optimality.     

Effects of laundry detergents on Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Euroglyphus maynei.

BACKGROUND: House-dust mites in clothing and bedding are the source of major allergens. Based on studies of Dermatophagoides pteronyssinus only, weekly washing in hot water is recommended to kill dust mites and remove allergens from clothing and bedding. However, in the United States, washing is most often done in warm or cold water, and other mite species are involved. OBJECTIVE: The purpose of this study was to investigate the lethal effects of various temperatures of hot water alone and hot, warm, and cold water containing detergents and chlorine bleach on Dermatophagoidesfarinae, D. pteronyssinus, and Euroglyphus maynei. METHODS: Mites were soaked in test solutions at various temperatures and for various lengths of time, allowed time to recover, and then analyzed for survival. RESULTS: D. farinae was the most temperature-sensitive and chlorine bleach-sensitive of the three species. In 50 degrees C water alone, 100% mortality for D. farinae was obtained in 10 minutes, whereas most D. pteronyssinus and E. maynei survived. However, 53 degrees C-soaks for 12 and 5 minutes were needed to kill all D. pteronyssinus and E. maynei, respectively. Laundry detergents at their recommended and doubled concentrations and chlorine bleach generally increased mite mortalities over water alone for the three species. Soaking for 4 hours in warm water containing various detergents alone induced mortalities of 19 to 50%, 2 to 35%, and 14 to 46% for D. farinae, D. pteronyssinus, and E. maynei, respectively. CONCLUSIONS: Washing bed linens weekly in warm water with a 4-hour presoak containing most detergents and bleach will kill most D. farinae and, depending on the detergent brand, moderate numbers of D. pteronyssinus. Four-hour soaks in warm water containing the recommended concentrations of various detergents alone also kills moderate numbers of D. farinae, D. pteronyssinus, and E. maynei. Therefore, the cumulative effect of weekly washing with long presoaks should significantly reduce mite levels over time in bed linens, particularly when mattresses and pillows are encased to prevent reinfestation.