Measurement of extravascular lung water in hemodialysis patients using blood ultrasound velocity and optical density dilution

In hemodialysis patients, volume homeostasis is an important clinical problem. The aim is to have patients at an ideal "dry weight" postdialysis, but current methods for accurately measuring dry weight are disappointing. Krivitski et al. (ASAIO J 1998;44:M535-M540) have described a novel technique whereby extravascular lung water (EVLW) may be measured using blood ultrasound velocity and electrical impedance dilution. They have tested this method in animals and achieved agreement between obtained versus gravimetric measurements. Isotonic saline is used as a nondiffusible indicator and hypertonic (5%) saline is used as a diffusible indicator. By injecting these solutions and following their transits through the cardiopulmonary circulation, a theoretic basis for the calculation of EVLW may be derived from the cardiac output, the water transferred to blood, the amount of sodium chloride moved from blood to lung, and the increase in blood osmolality measured at the moment of osmotic equilibrium. We have used this new technique to measure EVLW for the first time in humans in 18 stable hemodialysis patients with no cardiac problems. Measurements were carried out twice in each patient, the first early in dialysis, the second toward the end of a dialysis session where fluid removal took place. The values for EVLW were 260+/-49 ml early in dialysis and 230+/-48 ml late in dialysis. This fall of 30+/-45 ml was statistically significant (p = 0.011). EVLW normalized to body weight was 3.29+/-1.0 ml/kg early and 3.02+/-1.04 ml/kg late in dialysis, a nonsignificant difference (p - 0.073). The normalized EVLW values are almost identical to those obtained in animals (3.1+/-1.4 ml/kg) by Krivitski et al. (see above). We conclude that this new technique can conveniently and noninvasively give an estimate of EVLW in hemodialysis patients. The clinical value of this measurement has now to be determined.     

Effects of raloxifene on bone density,biomarkers, and histomorphometric and biomechanical measures in ovariectomized cynomolgus monkeys

OBJECTIVE: The purpose of this study was to determine the effect of raloxifene on bone density, strength, metabolism, and histomorphometric characteristics in ovariectomized cynomolgus monkeys. DESIGN: A prospective, longitudinal study was designed to examine the effects of conjugated equine estrogens (0.04 mg/kg, CEE) and raloxifene (1 or 5 mg/kg, R1 and R5, respectively) on bone density, biomarkers, histomorphometry, and strength. Control groups included ovariectomized and sham-operated monkeys. Treatment was initiated the day after ovariectomy and continued for 24 months. Bone biomarker data were collected at baseline and every 3 months after surgery. Bone mass was determined at baseline and every 6 months after ovariectomy. Iliac biopsies were collected at baseline and 16 months postovariectomy, and the second lumbar vertebra and left midshaft femur collected at necropsy were examined histomorphometrically. Bone biomechanical properties were determined for the right femur and vertebrae. RESULTS: Compared with the placebo-treated ovariectomized monkeys, the high-dose raloxifene group had lower levels of alkaline phosphatase, tartrate-resistant acid phosphatase, urinary CrossLaps (collagen degradation products), and greater bone mass in the lumbar vertebrae. In the endocortical compartment, the high-dose raloxifene group had significantly lower mineralizing surface, mineral apposition rate, and bone formation rate in the iliac biopsy collected at 16 months and lower bone formation rate in the second lumbar vertebra. Within the midshaft femur, low-dose raloxifene significantly decreased the osteonal and total bone formation rates and also prevented the decrease in Young's modulus induced by ovariectomy in the midshaft femur. CONCLUSIONS: High-dose raloxifene prevented the development of osteopenia in the ovariectomized monkey by reducing bone turnover, albeit to a lesser extent than CEE. Histomorphometric and biomarker data suggest that mechanisms underlying the effect of raloxifene differ somewhat from that of CEE.     

Cross talk between carbon monoxide and nitric oxide

Carbon monoxide and nitric oxide are two endogenously produced gases that can act as second messenger molecules. Heme oxygenase and nitric oxide synthase are the enzyme systems responsible for generating carbon monoxide and nitric oxide, respectively. Both carbon monoxide and nitric oxide share similar properties, such as the ability to activate soluble guanylate cyclase to increase cyclic GMP. It is becoming increasingly clear that these two gases do not always work independently, but rather can modulate each other's activity. Although much is known about the heme oxygenase/carbon monoxide and nitric oxide synthase/nitric oxide pathways, how these two important systems interact is less well understood. This review attempts to define the current known relationship between carbon monoxide and nitric oxide as it relates to their production and physiological function.     

Intentional use of the Hawthorne effect to improve oral hygiene compliance in orthodontic patients

The purpose of this study was to evaluate whether the home care of noncompliant adolescent orthodontic patients with "poor" oral hygiene could be improved through the use of a deception strategy designed to intentionally induce the Hawthorne effect. This effect is often cited as being responsible for oral health improvements of control groups that receive placebo treatments. It is thought that participating in and fulfilling the requirements of a study alters subjects' behavior, thereby contributing to the improvement. Forty patients with histories of poor oral hygiene were assigned, in a quasi-random fashion, to two groups. Experimental subjects (n = 20) were presented with a situation that simulated participation in an experiment. These included the use of a consent form; distribution of tubes of toothpaste labeled "experimental"; instructions to brush twice a day for two minutes using a timer; and a request to return unused toothpaste. Control subjects (n = 20) had no knowledge of study participation. Tooth surface area covered with plaque was used as a proxy measure of home care behavior. It was measured at baseline, three months, and six months. Mean percentages of tooth surface covered with plaque for the experimental and control groups were 71 (+/- 11.52) and 74 (+/- 11.46) at baseline; 54 (+/- 13.79) and 78 (+/- 12.18) at three months; and 52 (+/- 13.04) and 79 (+/- 10.76) at six months. No statistically significant difference (p > .05) was obtained between groups at baseline. Statistically significant differences (p < .05) were found between groups at three and six months. Significant differences (p < .05) were also found only for the experimental subjects between baseline and each of the two subsequent observation periods. The efficiency and potential effectiveness of this strategy suggest that additional research be conducted to assess oral health improvements and possible applications to the private practice setting.     

The use of magnification in a preventive approach to caries detection.

OBJECTIVE: The aim of this study was to demonstrate the effect of low-powered magnification on the accuracy of caries detection and to compare it to the accuracy of unaided vision. METHOD AND MATERIALS: Five dental models were prepared with extracted, unrestored, human permanent premolars, molars, and canines. Dental examinations were undertaken in simulated clinical conditions by seven dentists using both unaided and magnified vision. A true diagnosis was obtained by histologic sectioning, thereby allowing diagnostic accuracy to be calculated. RESULTS: The sensitivity of diagnosis, representing the percentage of diseased sites found correctly, was significantly greater when magnification was used. There was no statistically significant difference in the specificities, or percentages of correctly identified healthy sites, between magnification and unaided vision. CONCLUSION: Magnification, although not perfect, improved significantly on the accuracy of diagnosis and can therefore be recommended for caries detection.     

Wild-type and A328W mutant human butyrylcholinesterase tetramers expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicity

Human butyrylcholinesterase (BChE) hydrolyzes cocaine to inactive metabolites. A mutant of human BChE, A328W, hydrolyzed cocaine 15-fold faster compared with wild-type BChE. Although the catalytic properties of human BChE secreted by Chinese hamster ovary (CHO) cells are identical to those of native BChE, a major difference became evident when the recombinant BChE was injected into rats and mice. Recombinant BChE disappeared from the circulation within minutes, whereas native BChE stayed in the blood for a week. Nondenaturing gel electrophoresis showed that the recombinant BChE consisted mainly of monomers and dimers. In contrast, native BChE is a tetramer. The problem of the short residence time was solved by finding a method to assemble the recombinant BChE into tetramers. Coexpression in CHO cells of BChE and 45 residues from the N terminus of the COLQ protein yielded 70% tetrameric BChE. The resulting purified recombinant BChE tetramers had a half-life of 16 h in the circulation of rats and mice. The 16-h half-life was achieved without modifying the carbohydrate content of recombinant BChE. The protective effect of recombinant wild-type and A328W mutant BChE against cocaine toxicity was tested by measuring locomotor activity in mice. Pretreatment with wild-type BChE or A328W tetramers at a dose of 2.8 units/g i.p. reduced cocaine-induced locomotor activity by 50 and 80%. These results indicate that recombinant human BChE could be useful for treating cocaine toxicity in humans.     

Correlation of neurokinin (NK) 1 receptor occupancy in gerbil striatum with behavioral effects of NK1 antagonists

Interest in central neurokinin (NK) 1 receptors has increased based on reports of the therapeutic potential for NK1 antagonists in anxiety and depression. In these studies, an ex vivo binding procedure was used to correlate NK1 receptor occupancy in striatum by NK1 antagonists with their potency to inhibit NK1 agonist-induced foot tapping in gerbils (GFT). The following compounds were administered orally: CP-99,994 [(+)-cis-n-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine), L-742,694 [5-[[2(S)-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-3(S)-phenyl-4-morpholinyl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one]), MK-869 [5-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3(S)-(4-fluorophenyl)-4-morpholinyl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one], CP-122,721 [cis-n-[[2-methoxy-5-(trifluoromethoxy)phenyl]methyl]-2-phenyl-3-piperidinamine], L-760,735-F [4-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3(S)-(4-fluorophenyl)-4-morpholinyl]methyl]-N,N-dimethyl-1H-1,2,3-triazole-5- methanamine], GR205171 [N-[[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]phenyl]methy]-2(S)-phenyl-3(S)-piperidinamine], L-733,060 [(2S,3S)3-([3,5-bis(trifluoro methyl)phenyl]methoxy)-2-phenylpiperidine], and L-733,061 [(2R,3R)-3-([3,5-bis(trifluoromethyl)phenyl]methoxy)-2-phenylpiperidine]. Two hours later, gerbils received the NK1 agonist GR73632 [H(2)N-(CH(2))(4)-CO-Phe-Pro-NMe-Leu-Met-NH(2)] i.c.v. and foot tapping was measured for 5 min. The same procedure was used for ex vivo binding studies except that saline, rather than agonist, was administered i.c.v. before dissection of the striatum. The tissue homogenate was then used in an equilibrium radioligand binding assay. When IC(50) values for inhibition of ex vivo (125)I-substance P binding by NK1 antagonists were compared with the corresponding EC(50) values for inhibition of GFT, a significant positive correlation was observed (r(2) = 0.97, p < 0.001). This result indicates that increased NK1 receptor occupancy in striatum by NK1 antagonists parallels the inhibition of agonist-mediated GFT. For all compounds, the dose that produced the maximum inhibition of GFT resulted in less than 100% ex vivo receptor occupancy in striatum. When gerbils did not receive the i.c.v. saline injection before ex vivo binding, thereby leaving the blood-brain barrier (BBB) intact, the IC(50) values for antagonists were unchanged, suggesting that potential damage to the BBB caused by the i.c.v. injection did not affect determinations of antagonist potency in the GFT model.     

Surveying physicians: do components of the "Total Design Approach" to optimizing survey response rates apply to physicians?

BACKGROUND: Surveys serve essential roles in clinical epidemiology and health services research. However, physician surveys frequently encounter problems achieving adequate response rates. Research on enhancing response rates to surveys of the general public has led to the development of Dillman's "Total Design Approach" to the design and conduct of surveys. The impact of this approach on response rates among physicians is uncertain. OBJECTIVE: To determine the extent to which the components of the total design approach have been found to be effective in physician surveys. DESIGN: A systematic review. RESULTS: The effectiveness of prepaid financial incentives, special contacts, and personalization to enhance response rates in surveys of physicians have been confirmed by the existing research. There is suggestive evidence supporting the use of first class stamps on return envelopes and multiple contacts. The optimum amount for incentives and the number of contacts necessary have not been established. Details of questionnaire design and their impact on response rates have received almost no attention from researchers. Few studies have assessed the usefulness of combinations of components of the total design approach. CONCLUSIONS: Despite the number of surveys conducted among physicians, their cost, the level of interest in their findings, and in spite of inadequate response rates, there have been few randomized trials conducted on important aspects of enhancing response in this population. Until this gap has been filled, researchers conducting surveys of physicians should consider including all components of the total design approach whenever feasible.     

Assessment for depression among nursing home elders: evaluation of the MDS mood assessment

The 30-item Geriatric Depression Scale (GDS), the GDS Short Form, and the Mood Assessments from the Minimum Data Set versions 1 and 2 were completed for 50 nursing home elders. The purpose of the study was to evaluate agreement among these measures of depression, with the GDS considered the gold standard. Although the GDS Short Form performed highly consistently with the GDS, the correlations of the MDS mood assessments with the GDS were relatively low. The results are discussed in the context of the characteristics that surround the use of the MDS, and recommendations are made for improving methods of detecting depression among nursing home elders.