Identification of urinary metabolites of 8-methyl-8-azabicyclo- 3,2,1] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey.

The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to authentic standards. The major metabolite in the dog, approximately 41% of the administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On the other hand, the major metabolite in the monkey was the glycine conjugate of 3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL 72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little (less than 1%) of the parent compound was found in urine. The major pathways of metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and amino acid conjugation.     

Partial defluoridation of drinking water using fluorapatite precipitation.

Ion adsorption and ion exchange are two methods commonly used in small home units to treat drinking water to bring the fluoride concentration to within acceptable limits. However, the necessary flowthrough system is often difficult to arrange where there is no piped supply and gradual exhaustion of the active agent is not easily detected. In an attempt to overcome these problems a defluoridation method based on the precipitation of a sparingly soluble fluoride salt, fluorapatite, has been studied. Samples of simulated high-fluoride drinking waters, approximately 10 ppm F, were saturated with brushite, resulting in a state of supersaturation with respect to fluorapatite. Subsequent seeding with hydroxyapatite caused a lowering of the calcium, phosphate, and fluoride concentrations in solution, indicative of fluorapatite precipitation. Repeating the process had an additive effect. Bone char was a less effective seed than hydroxyapatite with water containing fluoride only, but was a more effective seed with simulated Kenyan borehole water containing additional salts. Sixty-minute brushite saturation and apatite seeding steps were generally more effective than 10-min steps. The results suggest that apatite coprecipitation may be a convenient low-technology way to defluoridate drinking water, although prior testing might be useful to ensure adequate removal of fluoride.     

Evaluation of endoscopic laser Doppler flowmetry for measurement of human gastric blood flow. Methodologic aspects

Endoscopic measurement of gastric blood perfusion by laser Doppler flowmetry (LDF) has been evaluated in 28 patients and 15 healthy volunteers. During the recordings it was necessary to keep the probe in light contact with the mucosa to obtain stable curves and to avoid artificial Doppler signals caused by relative movements between the gastric wall and the probe. Gastric distention by air insufflation did not influence the recorded flow level significantly when air insufflation was moderate. The intravenous injection of 0.6 mg atropine did not cause any significant alteration in recorded blood flow, and this drug may be used as premedication before endoscopic blood flow measurements. Recordings with both 4- and 12-kHz bandwidth of the LDF instrument showed a relative constant relationship for different flow levels, the flow values measured with 12 kHz being about twice the corresponding values measured with 4 kHz. With 12-kHz bandwidth more of the disturbance signal is recorded, which makes analysis of endoscopic recorded flow curves difficult and inaccurate. It is therefore recommended to use 4-kHz bandwidth during endoscopic measurements in conscious humans. Blood flow measurements from both sides of the gastric wall were consistently of the same order of magnitude (r = 0.91), and the endoscopically recorded output signal increased in three of five patients when a reflecting mirror was placed at the serosal side. The results indicate that endoscopic LDF usually represents blood perfusion in all layers of the gastric wall.     

A longitudinal study of semen quality in pesticide spraying danish farmers

It was hypothesized that occupational exposure to pesticides during a spraying season causes changes in semen quality that might be detected in a longitudinal study. We analyzed the within-person changes in semen quality and reproductive hormones across a spraying season in groups of farmers using and not using pesticides. A total of 248 men collected two semen samples (participation rate: 32%). The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups, unadjusted or adjusted. Only minor changes were found in sperm morphology, vitality, motility, sperm chromatin denaturation (SCSA), and reproductive hormones, and the differences in changes between the two groups were nonsignificant, or, in the opposite direction to the expected. There was no relation between the changes in sperm parameters in relation to pesticide exposure variables. In conclusion, use of pesticides by Danish farmers is not a likely cause of short-term effects on semen quality and reproductive hormones.     

What has trust got to do with it? Cardiac risk reduction and family physicians' discussions of evidence-based recommendations

The management of patients through the use of evidence-based medicine has become the 'mantra' of medicine within many Western countries. Evidence-based medicine is aimed at providing the best objective, scientific care to all patients, and reducing as far as possible patients' risks of disease and complications from disease. Based on family physicians' discussions of the use of evidence-based recommendations for two cardiac diseases, this paper explores how subjectively-based trust enters into family physicians' decision to use evidence-based medicine. In addition, we show how trust influences physicians' work of recommending evidence-based medicine to patients, and physicians' perceptions of why patients follow recommendations aimed at risk reduction. We conclude that although much of the current discussion about evidence-based medicine assumes a 'rational' model of physician behaviour based on the application of the 'best objective scientific' results, subjectively-based perceptions of trust influence physician practices, and point to the need to understand the power of relational issues in influencing physician practices even when utilizing evidence-based knowledge.     

Transplant Tolerance in Non-Human Primates: Progress, Current Challenges and Unmet Needs

Given the significant morbidity associated with current post-transplant immunosuppressive regimens, induction of immune tolerance continues to be an important goal of clinical organ transplantation. While many strategies for inducing tolerance have been successfully applied in murine models, significant barriers are faced when translating these approaches to the clinic. This has necessitated pre-clinical studies in the more closely related model system, the non-human primates (NHP). In this review, we will discuss the four most prominent strategies for inducing transplantation tolerance and highlight their relative success and shortcomings in NHP. These strategies are: (1) T-cell costimulation blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance induction through regulatory T-cells. After discussing the progress that has been made with each of these strategies, we will identify this field's most pressing unmet needs and discuss how we may best overcome the resulting barriers to tolerance induction.     

A blinded,controlled evaluation of anxiety and depressive symptoms in patients with fibromyalgia,as measured by standardized psychometric interview scales

The objective of the study was to evaluate the presence of psychopathology in fibromyalgia patients compared with a control group of other rheumatologic patients with pain. Forty-nine fibromyalgia patients and 33 control patients were interviewed blinded, using standardized psychometric scales. Pain was scored on a visual analogue scale. Fibromyalgia patients scored significantly higher than the controls on the Bech-Rafaelsen Melancholia Scale, the Atypical Depression Scale and the Hamilton Anxiety Rating Scale. On the Newcastle Depression Scale there was no difference. In both groups a correlation was found between pain score and psychometric scoring. The fibromyalgia patients scored significantly higher on pain than the controls. After correcting for this difference, the fibromyalgia patients still scored higher on anxiety and depression.     

Reliability of in situ measurements of colorectal polyps.

A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of the polyp the area of the polyp on the picture can be calculated by computerized analysis. To test the reliability and sensitivity of these two in situ measurements, 43 colonic polyps (mean diameter, 8.5 mm; range, 4-20 mm) removed by snare diathermy resection were examined. The maximal diameter was measured, and two Polaroid pictures taken of each polyp. After polypectomy each polyp was subjected to extracorporeal reassessment of diameter and measurement of weight and volume. By computerized analysis of the pictures the following variables were estimated: 1) area of the polyp on the picture; 2) largest diameter; 3) maximum width 90 degrees on the largest diameter; 4) maximum distance from centre of gravity; and 5) minimum distance from centre of gravity. Results showed good correlation between diameter measured in situ and after removal (r = 0.93), diameter raised to the 3rd power and weight (r = 0.93), and also to volume (r = 0.77). Area analysis compared with weight was less good (r = 0.72). A very high correlation was demonstrated between weight and volume (r = 0.99). We conclude that the measurement of diameter in situ with a measuring probe is sensitive and somewhat more reliable than computerized analysis of size. The present 3-year follow-up and intervention study will show which of the two methods is preferable for evaluation of polyp growth.     

Diagnosis of scaphoid fractures:A prospective multicenter study of 1,052 patients with 160 fractures

In a prospective multicenter study of 1,052 patients with clinical signs of a scaphoid fracture, mammo-graphic films and fine intensifying screens were used at the radiographic examination. 5 standardized projections including 3 special projections focused on the scaphoid were taken. 150 fractures were diagnosed at the first examination but in 10 cases the fracture was first diagnosed at a second radiographic examination after 10-14 days.

The second examination still seems mandatory despite the use of high quality radiographs with optimal spatial resolution and contrast, and the value of supplementary special projections.