Imaging of sacroiliitis in early seronegative spondylarthropathy. Assessment of abnormalities by MR in comparison with radiography and CT.

PURPOSE: To analyze the type and frequency of abnormalities of the sacroiliac joint (SIJ) in early seronegative spondylarthropathy (SpA) by MR in comparison with CT and radiography, assess the most appropriate MR sequences to be used, and introduce a new way of grading MR abnormalities of the SIJ. MATERIAL AND METHODS: The SIJs of 41 patients with early SpA (median duration of inflammatory low back pain of 19 months) were evaluated by MR imaging using STIR, T1, T2, and T1 fat saturated (FS) sequences before and after i.v. Gd contrast medium followed by staging of abnormalities. The findings were compared with those obtained by CT and radiography. RESULTS: MR and CT had equal efficacy superior to radiography in staging of erosions and osseous sclerosis. Only MR allowed visualization and grading of active inflammatory changes in the subchondral bone and surrounding ligaments in addition to bone marrow fatty accumulations. T2-weighted sequences did not contribute to assessment of sacroiliitis. CONCLUSION: MR of the SIJs is reliable in its visualization of joint erosions in early SpA and allows differentiation between active and chronic sacroiliitis. We recommend the following sequences: semicoronal T1 and both semicoronal and semiaxial STIR. If these images are normal, the examination can be finished; otherwise additional semicoronal T1 FS before and after i.v. contrast has to be performed as well as semiaxial post-contrast T1 FS.

Complications of dynamic graciloplasty: incidence, management, and impact on outcome.

PURPOSE: Dynamic graciloplasty can improve continence in patients with severe refractory fecal incontinence, but associated morbidity is high. The purpose of this study was to identify complications associated with dynamic graciloplasty and to characterize their treatment and impact on patient outcome. METHODS: In 121 patients enrolled in a prospective trial of 20 centers and eligible for safety analysis, all complications of dynamic graciloplasty were recorded at the time of their occurrence and followed up until resolution. Severe treatment-related complications were defined as those requiring hospitalization or surgical intervention. RESULTS: In 93 patients, 211 complications occurred. Of these, 89 (42 percent) in 61 patients were classified as severe treatment-related complications and resulted from the following: major infection, 19; minor infection, 10; thromboembolic events, 3; device performance and use, 13; pain, 16; noninfectious gracilis problems, 8; noninfectious wound-healing problems, 3; other surgery-related complications, 3. In addition, severe treatment-related complications resulted from constipation in ten and stoma creation or closure in ten. The recovery rate (full or partial) was 87 percent overall, and for severe treatment-related complications, was 92 percent. Of the types of complications, only major infections had an adverse effect on outcome. CONCLUSION: Severe complications occur frequently after dynamic graciloplasty, but are usually treatable. They often require one or more reoperations and can lead to significant delays in completion of therapy. In most cases therapy can be salvaged.

Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin.

BACKGROUND: Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging. METHODS AND RESULTS: Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles. CONCLUSIONS: Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.

An object-oriented framework for dynamic ecosystem modeling: application for integrated risk assessment.

Ecological risk assessment requires the integration of a wide range of data on anthropogenic processes, ecological processes and on processes related to environmental fate and transport. It is a major challenge to assemble a simulation system that can successfully capture the dynamics of complex ecological systems and an even more serious challenge to be able to adapt such a simulation to shifting and expanding analytical requirements and contexts. The dynamic information architecture system (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex simulations. DIAS supports simulations in which the real-world entities that make up ecological systems are represented as software 'entity objects'. The object-oriented integrated dynamic landscape analysis and modeling system (OO-IDLAMS) provides a good example of how DIAS has been used to build a suite of models for the purpose of assessing the ecological impacts of military land use and land management practices. OO-IDLAMS is a prototype conservation modeling suite that provides military environmental managers and decision-makers with a strategic, integrated and adaptive approach to natural resources planning and ecosystem management. The OO-IDLAMS prototype used Fort Riley, Kansas as a case study to demonstrate DIAS' capabilities to offer flexibility, interprocess dynamics and cost-effective reuse of code for ecosystem modeling and simulation. DIAS can also readily lend itself to other applications in ecological risk assessment. It has great potential for the integration of ecological models (associated with biological uptake and effects) with environmental fate and transport models. A DIAS ecological risk assessment application could be used to predict the magnitude and extent of ecological risks and evaluate remedy effectiveness in a timely and cost-effective manner.

Vaginal pudendal nerve stimulation: a new technique for assessment of pudendal nerve terminal motor latency.

BACKGROUND: To evaluate vaginal stimulation of the pudendal nerve, a new method for investigation of pudendal nerve terminal motor latency (PNTML) and to assess the reproducibility of the method. METHODS: Thirteen healthy women and 11 female patients, median age 31 years (range 21-53 years), participated in the study. Ten patients had sustained an anal sphincter rupture and one had idiopathic anal incontinence. Pudendal nerve terminal motor latency was measured after vaginal stimulation of the pudendal nerve with motor response from the pelvic floor and rectal stimulation with motor response from the anal sphincter using the St. Marks pudendal electrode. The women were stimulated by two observers both vaginally and by the rectum. RESULTS: Vaginal PNTML for observer 1 was 2.06 msec (0.50 msec, 2 s.d.) and 2.04 msec (0.55 msec, 2 s.d.) for observer 2, while rectal PNTML was 1.99 msec (0.56 msec, 2 s.d.) and 1.97 msec (0.54 msec, 2 s.d.) respectively. The difference between vaginal and rectal PNTML was 0.065 msec for observer 1 (p = 0.106) and 0.070 msec for observer 2 (p < 0.05). Degree of agreement between vaginal and rectal PNTML was 80%-116% for observer 1 and 84%-12% for observer 2 (100% represent total agreement between measurements). Interobserver reproducibility for vaginal PNTML was 90%-109% and 86%-113% for rectal PNTML. CONCLUSION: In clinical practice vaginal PNTML may replace rectal PNTML in women. Reproducibility is in the same range as for rectal PNTML.

Observer variability in the assessment of type and dysplasia of colorectal adenomas, analyzed using kappa statistics.

PURPOSE: The aim of this study was to establish the intraobserver and interobserver variability in the assessment of histologic type (tubular, villous, and tubulovillous) and grade of cytologic dysplasia (mild, moderate, and severe) in colorectal adenomas. METHODS: One hundred eighty-seven slides of adenomas were assessed twice by three experienced pathologists, with an interval of two months. Results were analyzed using kappa statistics. RESULTS: For agreement between first and second assessment (both type and grade of dysplasia), kappa values for the three specialists were 0.5345, 0.9022, and 0.4100, respectively. Agreement was better for type than for dysplasia. The strength of agreement was moderate for Observers A and C and almost perfect for Observer B. Agreement between all three observers was seen in 35.2 percent for both type and dysplasia in 61 percent for type and in 47.8 percent for dysplasia. The kappa values for Observer A vs. B and Observer C vs. B were 0.3480 and 0.3770, respectively (both type and dysplasia). Values for type were better than for dysplasia, but agreement was only fair to moderate. CONCLUSION: The interobserver agreement was moderate to almost perfect, but the intraobserver agreement was only fair to moderate. A simpler classification system or a centralization of assessments would probably increase kappa values.

Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults.

OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose-response study. PATIENTS: Eight GH-deficient adults, who received stable T4 substitution due to central hypothyroidism; two patients, who were euthyroid without T4 supplementation were studied separately. DESIGN: All patients were initially studied after at least 4 weeks without GH followed by 3 consecutive 4-week periods in fixed order during which they received daily doses of 1, 2 and 4 IU of GH/m2 body surface area. The patients were hospitalized for 24 hours at the end of each period. MEASUREMENTS: Circulating total and free concentrations of T4 and T3, total rT3 and TSH were measured once at the end of each study period. Circadian TSH levels were recorded during the period without GH and during GH treatment with 2 IU GH. RESULTS: Highly significant GH dose-dependent increases in total and free T3 and a reduction in rT3 were observed. The T3/T4 ratio also increased with increasing GH dosages (P < 0.001). In seven patients subnormal T3 levels were recorded in the period off GH, despite T4 levels well within the normal range. Resting energy expenditure also increased and correlated with free T3 levels (r = 0.47, P < 0.05). The circadian TSH levels exhibited a significant nocturnal increase during the period without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P < 0.05)). The two euthyroid non-T4 substituted patients exhibited qualitatively similar changes in all parameters. CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused a significant blunting of serum TSH. These findings suggest that GH plays a distinct role in the physiological regulation of thyroid function in general, and of peripheral T4 metabolism in particular.

Recent developments in 'any willing provider' legislation.

Because of recent state-level legislation, many health care networks may not be allowed to choose between qualified member providers. Gerald A. Neiderman, J.D., Jay D. Christiansen, J.D., and Kelly Phillips, J.D., of the health care practice group of Fagre & Benson, update the background, trends and potential impacts of any willing providers laws.

Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: a double-blind placebo-controlled study.

Growth hormone (GH) promotes protein anabolism and lipolysis. Its effects on glucose metabolism include suppression of glucose oxidation and may be associated with insulin resistance. In addition, GH stimulates energy expenditure (EE) and peripheral thyroid hormone metabolism. GH secretion is reduced in obese patients, but whether this is of pathophysiological significance is incompletely understood. In a double-blind placebo-controlled crossover design, we studied the effects of GH administration (0.03 mg.kg ideal body weight [IBW]-1.d-1) on fuel metabolism, EE, and thyroid function in 10 obese women (age, 30.4 +/- 2.4 years; body mass index [BMI], 37.0 +/- 2.8 kg/m2, mean +/- SE) with a normal prestudy oral glucose tolerance test (OGTT). Each treatment period (GH or placebo) lasted 5 weeks, separated by a 5-week washout period. At the end of each treatment period, subjects were studied in the basal state (8:00 AM) and during a euglycemic glucose clamp including indirect calorimetry and isotopic measurement of glucose turnover. Lean body mass (LBM) was assessed at the end of each period by dual-energy x-ray absorptiometry. In the basal state, GH induced a significant increase in circulating levels of free fatty acids (FFA), glucose, insulin, and C-peptide. This was associated with a significant increase in resting EE (kcal/24 h, 1,934 +/- 92 placebo v 2,323 +/- 134 GH, P < .001), a decrease in the respiratory exchange ratio (RER), and increased rates of lipid oxidation (mg.kg LBM-1.min-1, 1.55 +/- 0.09 placebo v 2.20 +/- 0.13 GH, P < .01). GH increased the rate of total basal glucose turnover, whereas oxidative glucose disposal was significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic anal manometry in the assessment of patients with obstructed defecation.

Patients with obstructed defecation show no consistent abnormalities when assessed by standard anorectal physiologic methods. With a recently developed technique for dynamic anal manometry, we studied 13 female patients with obstructed defecation and 20 healthy volunteers. Seven parameters of anal function were measured. There were no differences between the median values for the two groups. Seven patients (54 percent; 95 percent confidence limits, 25-81 percent) had anal compliance below the normal range, either during opening or closing of the sphincter at rest (five patients), during squeeze (one patient), or both (one patient). Opening and closing pressures of the sphincter at rest, maximal closing pressure during squeeze, and anal hysteresis were normal. Standard anal manometry did not show any differences between patients and controls. Rectal compliance was lower in patients with obstructed defecation, median difference 5 ml/cm H2O (95 percent confidence limits, 1-9 ml/cm H2O). In conclusion, the more detailed method of dynamic anal manometry shows that some patients with obstructed defecation have a less compliant anal sphincter and a less compliant rectum, but in many patients no abnormal findings can be made.

Clinical assessment of the anal continence plug.

Recently, promising results with different modifications of an anal continence plug were reported in a pilot study. We have performed a clinical assessment of the plug preferred by the majority of patients in this study in an ambulatory group of patients incontinent to liquid and solid stool. Nine of 14 patients (64 percent; 95 percent confidence interval: 35-87 percent) were continent when they used the plug. In 43 percent (18-71 percent), the plug occasionally slipped out, and 71 percent (42-92 percent) experienced discomfort to a varying degree, which caused 11 patients to withdraw from the study before the end of the planned study period. No correlation was found between the results of anorectal physiology studies and the benefit or inconvenience of using the plug. The overall conclusion is that the majority of patients would use the plug under special circumstances because it eliminates the fear of fecal leakage but that local discomfort, possibly due to the material, would prevent its daily use.

Beneficial effects of GH replacement therapy in adults.

Growth hormone deficiency in adults is associated with psychosocial maladjustment, reduced muscle strength, and reduced exercise capacity. Body composition is significantly altered, with increased fat and decreased muscle volume as compared with healthy subjects. Kidney function is subnormal. Epidemiological data suggest premature mortality owing to cardiovascular disease in hypopituitary patients. Short-term GH treatment trials have shown improved psychosocial performance, normalization of body composition, increased muscle strength, improved exercise capacity, increased cardiac performance, and normalization of kidney function. Thus GH replacement therapy in GH-deficient adults exhibits potential long-term beneficial effects. A number of important questions have to be addressed before long-term GH replacement therapy in GH-deficient adults can be considered on a routine basis.

A technique for the dynamic assessment of anal sphincter function.

A technique which renders continuous measurement of the cross-sectional area and pressure of the anal canal possible during distension and contraction of the anal sphincter has been developed. Electromyography of the external sphincter is measured simultaneously. With this technique a more detailed assessment of anal sphincter function is possible, including the opening and closing pressures of the sphincter at rest, anal compliance, anal hysteresis and the maximal closing pressure during squeeze. The results of in vitro measurements, measurements on 16 healthy subjects and 6 patients with faecal incontinence are presented.

Rectal compliance in the assessment of patients with fecal incontinence.

Rectal compliance (dV/dP) was studied in 31 patients with fecal incontinence, 8 patients with constipation, and 16 control subjects. Patients with fecal incontinence experienced a constant defecation urge at a lower rectal volume and also had a lower maximal tolerable volume and a lower rectal compliance than control subjects (median 126 vs. 155 ml, 170 vs. 220 ml, and 9 vs. 15 ml/mm Hg, respectively; P less than 0.05). Constipated patients had a higher constant defecation urge volume and maximal tolerable volume than controls (median, 266 ml and 300 ml; P less than 0.05). There was no differences in the parameters between patients with idiopathic fecal incontinence and patients with incontinence of traumatic origin, indicating that a poorly compliant rectum in patients with fecal incontinence may be secondary to anal incontinence due to the lack of normal reservoir function.

Follow-up of an activity-sensing, rate-modulated pacing device, including transtelephonic exercise assessment.

Single-chamber rate-modulated (ventricular or atrial demand [VVIR or AAIR]) pacemakers are now an accepted and frequently used pacing modality. Although several sensor-driven pacemakers are currently under investigation, activity-sensing pacemakers have been used most frequently to date. We assessed our implantation and follow-up experience with 156 activity-sensing pacemakers. Analysis of the patient population revealed an age range of 6 to 91 years and a variety of indications for pacing, the most common being atrioventricular block. Specific programming techniques were adopted for assessing these pacemakers. Although several episodes of reprogramming may be necessary to identify the optimal sensor settings for an individual patient, once optimal programming has been achieved, the sensing characteristics seem to have long-term stability. An important part of our follow-up procedure involves transtelephonic exercise, which allows some degree of long-term assessment of the sensor. All but six patients with pacemakers programmed to the sensor-driven mode (VVIR or AAIR) had evidence of sensor-driven pacing during transtelephonic exercise. Thus, this adjunct seems helpful for follow-up of some rate-modulated pacemakers.

An artificial betacell: assessment of the glucose analyser, infusion system and optimization of constants for the algorithms.

The glucose analyser and insulin infusion modules of the Biostator were tested. The infusion system was reliable since more than 99% of the computed volume of insulin solution was delivered by the infusion pump at infusion rates above 1/100 of maximum, and no insulin was adsorbed onto infusion bags or tubing. Blood glucose results from the Biostator were compared with routine laboratory methods during long-term feedback control. Both slope (0.73) and scatter (r=0.87) around the regression line were unsatisfactory when the recommended calibration procedure was used. Tests in fasting non-diabetic subjects showed a significant correlation between the variation in Biostator glucose read-out and the plasma protein concentration in the detector outflow. In diabetics the ratio between Biostator glucose read-out and laboratory glucose determinations declined significantly with time. These observations led to the introduction of a standardization procedure based on externally determined blood glucose concentrations. During long-term feedback experiments in diabetics this procedure resulted in a significant increase in slope (0.84) but no improvement in scatter around the regression line. Repeated OGTTs revealed a set of constants for the algorithms, which enabled normal glucose tolerance to be achieved with smaller amounts of insulin.