Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients.

BACKGROUND: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection. METHODS: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine. RESULTS: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level. CONCLUSIONS: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.     

Evaluation of Enoxaparin Given before and after Operation to Prevent Venous Thromboembolism during Digestive Surgery: Play-the-Winner Designed Study

A total of 316 patients were included in a play-the-winner (PTW) designed study comparing the safety of enoxaprain started preoperatively versus postoperatively as prophylaxis against venous thromboembolism for digestive surgery. In a PTW-designed study the treatment of any next patient depends on the outcome of the previous patient. If successful, the next patient receives the same treatment, if not, the comparative regimen is given. Excessive bleeding according to specified criteria, severe adverse reactions, clinically detected deep venous thrombosis (DVT), or pulmonary embolism (PE) were criteria for classification as “loser.” The PTW design allocates most patients to the superior treatment. The main variable in PTW studies is the number of consecutive patients receiving the same treatment. In this study 163 patients were allocated to postoperatively started and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of “winners” was found to be 82.8% and 78.4% in the post- and preoperatively treated groups, respectively. No significant differences were found between the groups with regard to frequency of “winners” or the number of consecutive patients before change of treatment. The percentile of survival distribution did not detect superiority of any group. Prophylaxis against postoperative venous thromboembolism for digestive surgery using enoxaparin can safely be started preoperatively.     

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.     

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.     

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.