Short-term experience with early steroid withdrawal in African-American renal transplant recipients.

There are limited data on the results of early steroid withdrawal (ESW) in African-American (AA) renal allograft recipients. We examined short-term transplant outcomes in a retrospective, non-concurrent cohort study of 40 AAs who did not (ESW group), and 33 who did [steroid maintenance (SM) group] receive maintenance steroids after day 4 post-transplant. Patients received thymoglobulin (ATG) induction, mycophenolate mofetil, and tacrolimus or sirolimus. Data were analyzed using survival analysis methods and regression models. Patients in the ESW group were older, had lower current panel reactive antibody and fewer re-transplants, and received fewer doses of ATG. One-year graft survival and acute rejection (AR) rates were 100% and 13% in the ESW group and 97% and 15% in the SM group. After controlling for confounders, at 1 year, ESW was not associated with higher risk of graft loss, AR, or worse graft function, but was associated with less weight gain. The SM group had higher cholesterol levels at 3 months and higher risk of post-transplant diabetes mellitus. We did not observe any cases of subclinical rejection. This study suggests that ESW under modern immunosuppression is safe over the short term in at least a subset of AA recipients with risk profiles similar to those studied herein, and could be associated with improved outcomes.

Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain.

Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hafter endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (two- to threefold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (> 50%) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition (approx. 25% decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

Using light sensitometry to evaluate mammography film performance.

The performance of commercially available light sensitometers was compared with two other methods of x-ray sensitometry to determine whether commercially available sensitometers are viable for evaluating clinical performance of mammography film. X-ray sensitometry was performed using mammography screens that were modified to accommodate a graded optical step tablet (screen sensitometry). Finally, a means for performing intensity-scale x-ray sensitometry was configured (inverse-square sensitometry). Clinical mammography x-ray exposure conditions were used and film processing quality was closely monitored during the study. Statistical results for chi-square probabilities on the resulting contrast curves yielded good agreement for most of the configurations investigated. Comparison of film gradient versus optical density curves showed good agreement for maximum contrast values and the corresponding optical density for maximum contrast for three of the four screen-film combinations used when comparing light sensitometry to screen sensitometry. A similar comparison of light sensitometers to inverse-square sensitometry showed good agreement for maximum contrast, but less agreement for the corresponding optical density of maximum contrast. Based on these results, the authors concluded that commercially available sensitometers could be used to estimate clinical film performance for the screen-film systems tested. In particular they can be used to determine the range of optical densities that provide optimal film contrast.

Interday variation in vertical ground reaction force in clinically normal Greyhounds at the trot.

OBJECTIVE: To determine the effect of interday variation on vertical ground reaction force variables in dogs. ANIMALS: 52 clinically normal Greyhounds of either sex weighing between 22 and 35 kg. PROCEDURE: Dogs were led at a trot across a floor-mounted force platform to determine vertical ground reaction force variables (peak [PFz] and impulse [IFz]) from hind limbs. Data were collected from each dog on 3 consecutive days. Variance components were estimated, using maximal likelihood to evaluate contributions of interday variation within dogs and variation attributable to dogs and repetitions. An ANOVA was used to test significance of interday variation within dogs and day within dog interactions. RESULTS: PFz, IFz, or both differed significantly from day to day for 29 of 52 dogs. Only PFz differed significantly among days for 16 dogs, and only IFz differed among days for 5 dogs. The PFz and IFz differed significantly from day to day in 8 dogs. Using ANOVA, the difference for PFz and IFz among days within dogs was significant. CONCLUSIONS: Effect of day within dog variation (interaction) should be considered as a component in statistical models in which data from 1 day are evaluated against data from the same subject on another day. We propose a statistical model that incorporates an accommodation for interday variation. Investigators should determine the factors that affect their studies, including the extent of interday variation, and compensate for the variation attributable to each factor in the statistical models used to analyze their data.

Renal pedicle torsion after simultaneous kidney-pancreas transplantation.

BACKGROUND: Simultaneous kidney-pancreas transplantation has become a recognized therapy for type I diabetes mellitus patients with diabetic nephropathy, neuropathy, and retinopathy. In the vast majority of these procedures, both grafts are placed intraperitoneally, which reduces posttransplant morbidity. Recently, in some of our recipients, we noted renal dysfunction related to complications of the renal pedicle. Our objectives in this study were to identify the cause of this renal dysfunction and to prevent its occurrence in future recipients. STUDY DESIGN: We undertook a retrospective chart review of simultaneous kidney-pancreas recipients who experienced renal dysfunction related to renal pedicle complications. RESULTS: We found four recipients with renal dysfunction related to renal pedicle torsion, diagnosed by serial ultrasound scans and kidney graft biopsies. Early diagnosis allowed salvage of three kidney grafts, but one was lost after late diagnosis. CONCLUSIONS: A high level of suspicion is needed to diagnose renal pedicle torsion. If simultaneous kidney-pancreas recipients have recurrent renal dysfunction, and rejection has been excluded, serial ultrasound scans with color flow Doppler examinations are needed. Once the diagnosis is made, a nephropexy to the anterior abdominal wall is indicated to prevent further torsion and save the kidney graft. We recommend prophylactic nephropexy of left renal grafts if the renal pedicle is > or = 5 cm long and if there is a 2 cm or more discrepancy between the length of the artery and the vein.

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia.

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

Morphology and body composition predict ovipositional history of female smokybrown cockroaches (Dictyoptera: Blattidae) in the laboratory.

We tested the hypothesis that presence and color of shed follicles in ovarioles of smokybrown cockroaches, Periplaneta fuliginosa (Serville), were correlated with the number of oothecae deposited in the laboratory. There were no shed follicles in females not having oviposited, whereas all females that had deposited 1-4 oothecae had shed follicles or resorption bodies, and females that had deposited > or = 5 oothecae had only shed follicle cells in the base of ovarioles. Other important correlates of female age (days after adult eclosion) were abdominal fat-free, thoracic fat and fat-free masses, and leg fat mass. Oocyte length could be substituted for oocyte fat and fat-free mass because these variables were correlated with oocyte length. Crop mass and delay in dissection after oothecal deposition were not correlated to female age or number of oothecae. Mass of body fractions (fat and fat-free) increased as females deposited additional oothecae. A generalized linear model predicted that as thoracic fat mass increased the number of oocytes already deposited by a female increased. In addition, the model predicted that red follicles would be found in females having deposited 1-3 oothecae and yellow follicles were predicted to be found in females having deposited > 2 oothecae.

Blood chemistry changes in the rat induced by high doses of nitronyl free radical spin traps.

For greatest efficacy, it is desirable to use spin trapping agents in the highest concentrations possible. Fifty-four male Sprague-Dawley rats were used to explore the relative toxicity of four representative nitronyl spin traps at doses chosen on the basis of earlier lethality studies. Most studies were confined to the 3- to 6-h period following drug injection, because the behavioral signs of toxicity are most evident early after injection and because spin trapping studies would typically be performed within this time frame. Doses of spin trap were dissolved in a corn oil/buffer vehicle and injected intraperitoneally (i.p.). Toxic signs were recorded periodically, and at the time of euthanasia or spontaneous death a blood sample was collected by cardiac puncture for clinical chemistry analysis and a necropsy was performed. Both gross pathology and histopathological examination of the major organs were essentially negative in all cases, with no obvious evidence of cellular damage being observed. Neither DMPO (232 mg/100 g b.wt.) nor PBN (100 mg/100 g b.wt.) were lethal in the present study, while both M4PO (20 and 40 mg/ 100 g b.wt.) and PyOBN (100 and 200 mg/100 g b.wt.) were lethal. Abnormal clinical chemistry findings were generally confined to those animals that died spontaneously or were euthanized early for humane reasons. In most cases, death was associated with marked seizure activity and impaired respiration, and deaths occurred within a few min to a few hours. The mechanism of toxicity was unclear due to the lack of histopathological evidence and the wide range of abnormal serum analytes in those rats killed by either M4PO or PyOBN. In conclusion, during the first 6 h after IP administration there is little indication of tissue damage by the nitrone spin traps until the dose is increased to a lethal level, at which point an acute, rapidly occurring, wide-spread disruption of tissue integrity seems to occur.

Redistribution of vertical ground reaction force in dogs with experimentally induced chronic hindlimb lameness.

When lameness occurs in a load-bearing limb, compensatory load adjustments are made in the other supporting limbs. The vertical component of the ground reaction force, as measured by force platform analysis, reflects these adjustments. This study describes the pattern of vertical ground reaction force redistribution during experimental, chronic hindlimb lameness in dogs. The peak and impulse of the vertical ground reaction force were measured and described in 13 dogs before, and at 2, 6, and 12 weeks after transection of the cranial cruciate ligament. These variables were compared among limbs. The vertical ground reaction force in the forelimbs did not change significantly during the course of the study. At 2, 6, and 12 weeks after surgery, means of peak vertical force in the limb that underwent surgery were 18.9%, 44.0%, and 61.3% respectively, of presurgical values. In the contralateral limb, corresponding values were 131.7%, 112.8% and 112.9% respectively. If one accepts the relationship of mechanical loading to musculoskeletal architecture and the now certain relationship between lameness and compensatory loading of other limbs, then the use of another limb of the same animal as a control is a potential study design flaw.

Control of Ia afferent input to triceps surae (soleus) locomotor nucleus precedes agonist muscle activation during gait.

Modulation of the triceps surae (soleus) H-reflex was investigated during treadmill walking to elucidate the temporal relationship between reflex facilitation and initiation of agonist muscle activation. Constant effective stimulation of the tibial nerve evoked the H-reflex. Contact foot switches monitored phases of the gait cycle. H-reflex changes were assessed at predetermined intervals across a window that anticipated the onset of soleus muscle electromyographic (EMG) activation. In five of six healthy subjects, multiphase statistical models revealed a 'breakpoint', reflecting a significant rise in H-reflex amplitude, beginning with stimuli delivered 144.1, 142.9, 148.8, 186.4 and 140.5 ms, respectively, prior to mean onset of EMG activity in the soleus muscle. In the sixth subject, no breakpoint was identified although the H-reflex amplitude gradually increased across the analysis window. These findings suggest that facilitation of the H-reflex is established well in advance of the descending corticomotoneuronal command to recruit spinal motoneurons in the motor act (i.e. prior to threshold spinal motoneuron depolarization). It is argued that a central programme controlling afferent input to the locomotor nuclei is part of the 'preparatory set' which precedes execution of the motor act.

Study of reproducibility of spin trapping results in the use of C-phenyl-N-tert-butyl nitrone (PBN) for trichloromethyl radical detection in CCl4 metabolism by rat liver microsomal dispersions. Biological spin trapping I.

The well-known metabolism of CCl4 to trichloromethyl radicals in rat liver microsomal dispersions has been reinvestigated with the goal to determine the repeatability and reproducibility of the EPR signal intensity of the EPR spectrum of the CCl3 adduct of PBN. It was found that at least eight repeat experiments were needed under identical conditions to obtain an average value with an error of +/- 10%. When the effect of changing the concentrations of CCl4, PBN or NADPH-generating system was investigated, the plots of EPR signal intensity vs. the variable selected showed initial smooth increases in signal strength with respect to an increase in concentrations of CCl4, PBN or NADPH-generating system. However, considerable scatter was found after the initial slope and only general trends could be recognized. It is concluded that with CCl4, no increase in EPR signal is found after 10 mM concentration. For PBN, the optimum concentration is about 30 mM. The signal strength seems to increase with increased amounts of NADPH generating system although with diminishing slope.

Comparison of aural infrared with traditional rectal temperatures in children from birth to age three years.

Glass-mercury rectal temperatures were compared with aural temperatures ("rectal equivalent" mode) in 234 children from birth to age 36 months. Sixty-two percent of measurements were divergent by at least 0.3 degrees C, 35% by greater than 0.6 degrees C. The aural infrared thermometer cannot be recommended for these ages; measurements were unacceptably inaccurate.

Baseline characteristics of subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) with fluvastatin.

A total of 429 subjects (79 women and 350 men), aged 35-75 years, have been enrolled in a randomized clinical trial of fluvastatin therapy for hypercholesterolemia. The progression and regression of atherosclerotic lesions will be assessed by quantitative angiography and positron emission tomography (PET) after 2.5 years of treatment. Patients were included in the trial if they had angiographically documented lesions that occluded 30-75% of the diameter of a major coronary vessel. Of the 429 subjects, 99 were also studied by PET at rest and during static exercise of sustained handgrip combined with administration of dipyridamole. All subjects were instructed in an American Heart Association/National Cholesterol Education Program (AHA/NCEP) Step I or Step II diet. Of the total, 107 subjects (25%) had low density lipoprotein cholesterol (LDL-C) > or = 160 mg/dL and were given cholestyramine, 8 g/day. All subjects were randomized to placebo or fluvastatin, the newest 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor to be introduced into the U.S. market. Fluvastatin is entirely synthetic and is similar in efficacy to the other available HMG-CoA reductase inhibitors. Its pharmaceutical profile (i.e., low systemic exposure) makes fluvastatin a good candidate for use in combination lipid-lowering therapy. The majority of subjects were recruited through a community campaign and the remainder through cardiac catheterization laboratories and the medical records of hospitals in the Texas Medical Center. Approximately 8,500 prospects from the community campaign were screened and 272 were randomized, a conversion rate of approximately 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronobiologic evaluation of blood pressure in school children.

Blood pressure (BP) and heart rate (HR) data were collected over 24 h with an ambulatory BP monitor to (a) determine the existence of 12-, 24-, and combined 12- and 24-h BP patterns in children as previously noted for adults; (b) provide MESOR (an acronym for midline estimating statistics of rhythm), amplitude, and acrophase data for subgroups of students by race and gender; and (c) determine the influence of HR (as an estimate of activity) on BP and BP patterns for 100 normal, healthy students 9-12 years of age. We found no statistically significant differences between various racial groups or between gender for MESOR, amplitude, acrophase, or degree of sinusoidality of circadian rhythmicity (R2 values) for BP; clinically interesting differences were observed, including lower MESOR BPs in Hispanic males when compared with their female counterparts and slightly higher MESOR BPs in blacks of both genders when compared with whites. In addition, we demonstrated subgroups of students who exhibited specific 24-h and combined 12- and 24-h patterns. Also, 67% of subjects showed stable or nonrhythmic BP patterns, perhaps related to BP sampling intervals. Differences in HR, as a surrogate measure of activity, accounted for 56% of the variation in systolic BP but only 26% in diastolic BP over the 24 h.

Changes in circadian rhythm of blood pressure in on-call pediatric residents.

To provide an objective measure of the effects of on-call stress on the blood pressure (BP) of a group of pediatric residents, we used a SpaceLabs Ambulatory Blood Pressure Monitor (ABPM) to compare 37 pediatric residents' on- and off-call BPs. Residents wore the ABPM for 24 h (once on call and again off call) to assess systolic and diastolic BPs every 30 min during the day and hourly overnight. We found significantly higher MESOR (an acronym for midline estimating statistic of rhythm, which yields a mean value more representative of the true mean than an average of a series of measurements) BPs and BP loads (%BP readings > 135 mm Hg for systolic and/or 85 mm Hg diastolic) during the on-call period. Some residents became hypertensive on call, and the normal 24-h pattern of lower nighttime blood pressures was altered during this period. ABPM monitoring may prove useful in evaluating the effectiveness of interventions to reduce the stress of residency training.

Enalapril in the prevention of restenosis following intracoronary intervention in a swine model.

BACKGROUND: Restenosis following percutaneous transluminal coronary angioplasty continues to be a major limitation of the procedure. To test whether an angiotensin-converting enzyme inhibitor may reduce restenosis, this study utilized an atherosclerotic, stented, Hanford miniature swine model of restenosis. METHODS: Each animal first was started on an atherogenic diet and had balloon abrasion of the left anterior descending and right coronary arteries. Four months later, balloon-mounted coil stents were placed into the abraded coronary arteries of each animal. Twenty-four animals then were randomly assigned to one of two groups: enalapril, and control. The enalapril group received 50 mg orally twice daily starting 1 week before intracoronary stenting. RESULTS: Follow-up 2 months later revealed angiographic stenosis in the control group of 30% +/- 13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/- 9%/20% +/- 11% in the enalapril group (P = not significant). The change in minimal lumen diameter from immediately after stenting to follow-up was not significantly different between control and enalapril groups. Area stenosis and maximal intimal thickness obtained by morphometric analysis were also compared, and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/- 16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns. There was no statistical difference. CONCLUSIONS: Enalapril fails to reduce restenosis in this animal model.

Comparison of temperature measurements by an aural infrared thermometer with measurements by traditional rectal and axillary techniques.

OBJECTIVE: To compare temperatures obtained with glass-mercury axillary and aural infrared thermometers with temperatures obtained with glass-mercury rectal thermometers. DESIGN: Blind comparison with criterion standard. SETTING: Well-baby nursery at a private teaching hospital. PATIENTS: Convenience sampling of 200 term newborn infants. INTERVENTION: Temperatures were measured simultaneously with glass-mercury rectal and axillary thermometers for a 3-minute period by one investigator. In a blinded fashion, a second investigator obtained three aural temperatures by using two tympanic membrane thermometers. One tympanic membrane reported infants' rectal-equivalent temperatures, and a second reported oral equivalent temperatures. RESULTS: Temperatures obtained with glass-mercury rectal and axillary thermometers for the population were similar (37 degrees +/- 0.4 degree C vs 36.8 degrees +/- 0.3 degrees C, respectively), but 25% of measurements at these two sites differed by > 0.3 degree C. Oral-equivalent tympanic membrane temperatures were more accurate than rectal-equivalent temperatures in predicting an infant's glass-mercury axillary and rectal temperatures (75% of oral-equivalent temperatures vs fewer than 50% of rectal-equivalent temperatures were within 0.3 degree C of either glass-mercury rectal or axillary measurements). CONCLUSIONS: Temperatures obtained with glass-mercury axillary and rectal thermometers are similar in most cases. However, temperatures obtained with tympanic membrane thermometers either in the rectal-equivalent mode or in the oral-equivalent mode did not accurately reflect an infant's rectal or axillary temperature. We believe that tympanic membrane temperatures should not be substituted for rectal or axillary temperatures in assessments of newborn infants.