Role of substance P in several models of bladder inflammation

Substance P (SP) is a peptide found in the sensory nervous system which has multiple biologic effects including stimulation of muscle contraction, pain nociception, immune cell functions, plasma extravasation and a constellation of inflammatory effects. Here we investigate the role of SP in several animals models of bladder inflammation. Using the female Lewis rat, inflammation was induced using either xylene, lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (polyIC). Inflammation occurred rapidly (4 h) and was maintained in each model for at least 7 days. Each of these protocols decreased the bladder content of immunoreactive SP by approximately 50%, suggesting enhanced release. There was no change in the urinary frequency of these animals over 3 weeks, suggesting that urinary frequency changes are not mediated by acute inflammation. We also found that the SP receptor (NK₁) antagonist, (?)CP96345, was unable to block the inflammation produced by polyIC, suggesting that SP is not an obligatory mediator of immune cell stimulation in this model.     

Computed tomography in gunshot wounds to the neck: Can we predict vascular injury?

The purpose of this study was to evaluate the ability of helical computed tomography (CT) to detect arterial injuries in gunshot wounds to the neck. In a blinded retrospective review, 54 helical CT scans of the cervical spine were evaluated for bullet/bone fragments, subcutaneous air, bullet path, hematoma, spine fractures, and pharyngoesophageal compromise. The distance of fragments to a major vessel was calculated. CT findings that correlated significantly with major arterial injury included the presence of fragments (bullet/bone) close to a major vessel (2.5 mm) and spine fractures. Visualizing fragments <5 mm from a vessel or a transcervical bullet trajectory predicted 12 of 13 major arterial injuries. We conclude that CT clearly depicts anatomic damage. Specific findings, such as the location of fragments and bullet trajectory adjacent to a vessel and spine fractures, indicate a higher probability of vascular damage, thus directing more definitive evaluation.     

Angioedema due to angiotensin-converting enzyme inhibitor use: Radiographic findings in 3 patients

Angioedema of the oropharynx and hypopharynx due to oral angiotensin-converting enzyme (ACE) inhibitors is a potentially life-threatening event and has not been well described in the radiology literature. A retrospective review of the clinical and radiologic findings in three patients with angioedema due to ACE inhibitor use was performed.Our subgroup of patients treated with ACE inhibitors presented with varying degrees of dysphagia, dyspnea, and facial swelling. Plain radiographic findings included enlargement of the epiglottis, aryepiglottic folds, and prevertebral and submental soft tissue. Computed tomography confirmed extensive retropharyngeal and subcutaneous edema. Clinical symptoms resolved in each case in 24–48 hours with cessation of the ACE inhibitor and concomitant steriod therapy.Our cases demonstrate the typical clinical and radiographic presentation of neck angioedema in the setting of ACE inhibitor use. As ACE inhibitors are increasingly being used as first-line agents in the treatment of hypertension, we caution that neck angioedema may be encountered with increased frequency in adults. Early recognition and immediate intervention result in rapid resolution of this potentially life-threatening event.     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

Genes in idiopathic calcium oxalate stone disease

An examination of the urinary excretions of 101 normal subjects indicated that the major genetic influence on calcium excretion is a codominant pair of alleles giving rise to three phenotypes, low, intermediate and high (hypercalciuric) excretors. This inference was based on variance, Hardy-Weinberg and segregation analyses. Similar independent gene pairs also appear to influence oxalate and citrate excretion, A 3-locus Hardy-einberg table using estimates of gene frequencies derived from the study of normals suggests that only 3 or 4 leading genes are involved in oxalate stone disease. Strong candidate genes identified from molecular and physiological studies cannot be proposed at present, but it is assumed that they influence the transport of these ions in either the intestine, kidney or both organs. The identification of the genes involved should be facilitated by the reduction of dietary influences on urinary excretions through the use of formula diets.     

Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

Reoperative Thyroid Surgery

Reoperative thyroid surgery is an uncommon operation associated with a high complication rate. We retrospectively reviewed the data of 115 patients to study the incidence of complications after reoperative thyroid surgery. There were 107 women and 8 men (13.4:1.0) with an average age of 42.8 years (range 18–80 years). The most frequent indication for reoperation was completion thyroidectomy for a carcinoma identified by permanent sections (50 patients, 43.5%). Reoperative surgery was performed on 13 (11.3%) patients with recurrent thyroid cancer. The remaining 52 patients underwent reoperation for recurrent thyrotoxicosis (12 patients, 10.4%), recurrent nodular goiter (28 patients, 24.3%) or recurrent multinodular goiter (12 patients, 10.4%). Seven patients with recurrent nodular goiter and one patient with recurrent thyrotoxicosis underwent total thyroidectomy for the presence of malignancies that were identified by frozen sections. Overall, the interval between the initial and reoperative procedures ranged from 1 day to 33 years (2335 ± 272 days). The length of hospital stay was 5.8 ± 0.5 days. The length of time needed for reoperative thyroid surgery was 122.0 ± 6.2 minutes. There was no 30-day perioperative mortality. The postoperative complications consisted of transient hypoparathyroidism in six patients (5.2%), permanent hypoparathyroidism in two patients (1.7%), transient RLN palsy in 3 patients (2.6%), and permanent recurrent laryngeal nerve palsy in two patients (1.7%). Reoperative thyroid surgery can be performed safely with little morbidity to the patient.