High stroke volume para-aortic counterpulsation device versus centrifugal pump in cardiogenic shock: experimental study

During the last decades a number of left ventricular assist devices has been used especially for patients resistant to pharmacologic treatment and to intraaortic balloon pump (IABP) support for left ventricular failure. A high stroke volume para-aortic counterpulsation device (PACD) has been developed utilizing the principle of the diastolic counterpulsation technique. In this study the hemodynamic effects of the valveless PACD were compared to those of the centrifugal blood pump (CBP) in nine dogs in acute experimental cardiogenic shock. Hemodynamic measurements were obtained at baseline with both devices off, PACD on and CBP off, or PACD off and CBP on. There was no difference in mean aortic pressure between PACD on (60.0 +/- 11.5 mmHg) and CBP on (69.0 +/- 26.8 mmHg). Similarly, there was no difference in left ventricular end-diastolic pressure with the PACD on (11.9 +/- 5.4 mmHg) versus the CBP on (9.9 +/- 5.2 mmHg) or the cardiac index with the PACD on (84 +/- 36 ml/kg/min) versus the CBP on (77 +/- 36 ml/kg/min). However, the left ventricular systolic pressure (55.0 +/- 19.0 with PACD versus 73.0 +/- 26.0 with CBP,p < 0.001), the tension time index (712 +/- 381 versus 1333 +/- 694,p < 0.01), and the double product (5629 +/- 2574 versus 7440 +/- 3294,p < 0.01) were significantly lower during assistance with the PACD than with the CBP. It was concluded that PACD is at least as effective as CBP for restoring hemodynamic status during acute experimental cardiogenic shock. Moreover, the PACD unloads the left ventricle more effectively than CBP, making it suitable for left ventricular mechanical support in cases with reversible myocardial damage.     

Biological production of semisynthetic opiates using genetically engineered bacteria

Semisynthetic derivatives of morphine and related alkaloids are in widespread clinical use. Due to the complexity of these molecules, however, chemical transformations are difficult to achieve in high yields. We recently identified the powerful analgesic hydromorphone as an intermediate in the metabolism of morphine by Pseudomonas putida M10. Here we describe the construction of recombinant strains of Escherichia coli that express morphine dehydrogenase and morphinone reductase. These strains are capable of efficiently transforming the naturally occurring alkaloids morphine and codeine to hydromorphone and the antitussive hydrocodone, respectively. Our results demonstrate the potential for recombinant DNA technology to provide biological routes for the synthesis of known and novel semisynthetic opiate drugs.     

Perfluorochemical liquid ventilation: from the animal laboratory to the intensive care unit

Perfluorochemical or perfluorocarbon liquids have an enormous gas-carrying capacity. During tidal liquid ventilation the respiratory medium of both functional residual capacity and tidal volume is replaced by neat perfluorocarbon liquid. Tidal liquid ventilation is characterized by convective and diffusive limitations, but offers the advantage of preserved functional residual capacity, high compliance and improved ventilation-perfusion matching. During partial liquid ventilation only the functional residual capacity is replaced by perfluorocarbon liquid. Both tidal and partial liquid ventilation improve gas exchange and lung mechanics in hyaline membrane disease, adult respiratory distress models and meconium aspiration. Compared to gas ventilation, there is less histologic evidence of barotrauma after liquid ventilation. Cardio-pulmonary interaction, inherent to the high density of liquid, and long term safety need further study. However, extrapolating from animal data, and taking into account promising human pilot studies, liquid ventilation has the desired properties to occupy an important place in the therapy of restrictive lung disease in man.     

Southeast Asians: Asian-Pacific Americans at risk for substance misuse

Projections indicate that by the year 2000 over a million Cambodians, Laotians, and Vietnamese will be living in the United States. There is sparse information relative to the use of substances by these groups due to the absence of national prevalence data. The combined stressors that these refugee groups have faced puts them at high risk for substance misuse. Southeast Asians infrequently use substance misuse and mental health services, which has been perceived as a lack of need for services by these groups. In reality, there is a critical shortage of culturally-appropriate treatment and intervention programs as the prevalence of substance misuse increases in these populations.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Non-extraction therapy in maxillary deficiency cases

Combined orthodontic and surgical management of maxillary deficiency with a Class III profile has accomplished efficient treatment and predictable results. Also, orthodontic/orthopedic therapy can give good results; but, in any case, if one of either or a combined therapy is selected, the orthodontist has to be sure of the correct diagnosis. The cephalometric analyses have to be done with care as it is possible to find contradictions among different analyses, especially in the A/P aspect. The Wits appraisal shows good capacity for determining the antero-posterior maxillomandibular relationship because it is sensitive to the osseous dimensional variants and lower anterior facial height. Nevertheless, it is a supplementary evaluation requiring additional data for the localization of the deformity.     

Evidence for a functional role of the dynamics of glycine-121 of Escherichia coli dihydrofolate reductase obtained from kinetic analysis of a site-directed mutant

Two-dimensional heteronuclear (1H-15N) nuclear magnetic relaxation studies of dihydrofolate reductase (DHFR) from Escherichia coli have demonstrated that glycine-121 which is 19 A from the catalytic center of the enzyme has large-amplitude backbone motions on the nanosecond time scale [Epstein, D. M., Benkovic, S. J., and Wright, P. E. (1995) Biochemistry 34, 11037-11048]. In order to probe the dynamic-function relationships of this residue, we constructed a mutant enzyme in which this glycine was changed to valine. Equilibrium binding studies indicated that the Val-121 mutant retained wild-type binding properties with respect to dihydrofolate and tetrahydrofolate; however, binding to NADPH and NADP+ was decreased by 40-fold and 2-fold, respectively, relative to wild-type DHFR. Single-turnover experiments indicated that hydride transfer was reduced by 200-fold to a rate of 1.3 s-1 and was the rate-limiting step in the steady state. Interestingly, pre-steady-state kinetic analysis of the Val-121 mutant revealed a conformational change which preceded chemistry that occurred at a rate of 3.5 s-1. If this step exists in the kinetic mechanism of the wild-type enzyme, then it would be predicted to occur at a rate of approximately 2000 s-1. Glycine-121 was also changed to alanine, serine, leucine, and proline. While the Ala-121 and Ser-121 mutants behaved similar to wild-type DHFR, the Leu-121 and Pro-121 mutants behaved like Val-121 DHFR in that hydride transfer was the rate-limiting step in the steady state and a conformational change preceding chemistry was observed. Finally, insertion of a glycine or valine between amino acids 121 and 122 produced mutant enzymes with properties similar to wild-type or Val-121 DHFRs, respectively. Taken together, these results provide compelling evidence for dynamic coupling of a remote residue to kinetic events at the active site of DHFR.     

Evaluation of the premier EHEC assay for detection of Shiga toxin-producing Escherichia coli

An enzyme-linked immunosorbent assay for the detection of Shiga toxins (Premier EHEC assay; Meridian Diagnostics, Inc.) was compared to conventional sorbitol-MacConkey culture for the recovery of enterohemorrhagic Escherichia coli. A total of 74 enteric pathogens, including 8 E. coli O157:H7 isolates, were recovered from 974 stool specimens. Two of these specimens were not tested by Premier assaying due to insufficient sample and are not considered in the data analysis. The Premier EHEC assay detected the 6 evaluable specimens which were culture positive for E. coli O157:H7 and identified an additional 10 specimens as containing Shiga toxin. Seven isolates were recovered from these 10 specimens by an immunoblot assay and were confirmed as toxin producers by a cytotoxin assay. Of these seven, four isolates were serotype O157:H7, one was O26:NM, one was O6:H-, and one was O untypeable:H untypeable. Three specimens contained Shiga toxin by both EHEC immunoassaying and cytotoxin testing; however, no cytotoxin-producing E. coli could be recovered. The sorbitol-MacConkey method had a sensitivity and a specificity of 60 and 100%, respectively, while the Premier EHEC assay had a sensitivity and a specificity of 100 and 99.7%, respectively, for E. coli O157:H7 only. The Premier EHEC assay also detected an additional 20% Shiga toxin-producing E. coli (STEC) that were non-O157:H7. Thus, the Premier EHEC assay is a sensitive and specific method for the detection of all STEC isolates. Routine use would improve the detection of E. coli O157:H7 and allow for determination of the true incidence of STEC other than O157:H7. The presence of blood in the stool and/or the ages of the patients were poor predictors of the presence of STEC. Criteria need to be determined which would allow for the cost-effective incorporation of this assay into the routine screen for enteric pathogens in high-risk individuals, especially children.     

Hip fracture prediction in elderly men and women: validation in the Rotterdam study

The aim of our study was to validate a hip fracture risk function, composed of age and femoral neck bone mineral density (BMD). This estimate of the 1-year cumulative risk was previously developed on the basis of Dutch hip fracture incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged 55 years and over was followed for an average of 3.8 years. The 1-year hip fracture risk estimate was calculated for each participant according to the risk function and categorized as low (<0.1%), moderate (0.1 to < 1%), or high (> or =1%). Observed first hip fracture incidence was then analyzed for each of these risk categories by age and gender. Additionally, we calculated the relative risk per standard deviation (SD) decrease in femoral neck BMD in this population. At baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk, and 378 as high risk During follow-up, 110 first hip fractures were observed corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95% confidence interval 3.4-5.0). The observed incidence rate in the low risk group was 0.2/1000 pyrs (0.1-0.9), 2.7/1000 pyrs (1.8-3.9) in the moderate risk group, and 18.4/1000 pyrs (12.4-27.2) in the high risk group. Below the age of 70 years, incidence was low in all categories, and very few individuals were considered at high risk Above the age of 70 years, the observed incidence was high in the high risk group, while in the low and moderate risk groups, the incidence remained low even over 80 years of age. In women, the age-adjusted relative risk for hip fractures was 2.5 per SD decrease in femoral neck BMD (1.8-3.6), while in men this relative risk was 3.0 per SD (1.7-5.4). In conclusion, we observed a similar relation of hip fracture with femoral neck BMD in men and women and were able to predict accurately hip fracture rates over a period of almost 4 years.