Spinal nerve ligation increases alpha2-adrenergic receptor G-protein coupling in the spinal cord

Intrathecal and epidural administration of the alpha2-adrenergic receptor agonist clonidine in humans results in analgesia to both acute nociceptive and chronic neuropathic pain. The potency of clonidine increases with hypersensitivity to mechanical stimuli after nerve injury, although the reasons for this change are unknown. In the present study, we tested the hypothesis that peripheral nerve injury alters either spinal alpha2-adrenergic receptor-mediated G-protein activity or alpha2-adrenergic receptor number. Rats were randomized to left spinal nerve ligation (SNL) or sham surgery. Tactile hypersensitivity in the hindpaw was confirmed and lumbar spinal cords were removed for binding assays. To examine agonist-induced G-protein coupling, [35S]GTP gamma S binding experiments were performed in spinal cord membranes and sections using norepinephrine as an alpha2-adrenergic agonist. SNL was associated with an increase in maximal efficacy, but not potency, of norepinephrine-stimulated [35S]GTP gamma S binding in dorsal horn. SNL had no effect on basal [35S]GTP gamma S binding or on muscarinic cholinergic-stimulated [35S]GTP gamma S binding. [35S]GTP gamma S autoradiography showed that this increase in alpha2-adrenergic-activated G-proteins occurred both ipsilateral and contralateral to SNL surgery. SNL did not alter total alpha2-adrenergic receptor number or affinity to [3H]-rauwolscine binding, and displacement studies with the alpha2A-adrenergic antagonist BRL44408 revealed that most of the binding was associated with the alpha2A-adrenergic subtype. These data suggest that the increased potency of clonidine in neuropathic pain could reflect increased efficiency of G-protein coupling from spinal alpha2-adrenergic receptors.     

Skinned single fibers from normal and dystrophin-deficient dogs incur comparable stretch-induced force deficits

Intact dystrophin-deficient canine muscles were previously shown to incur greater-than-normal stretch-induced force deficits. Here we tested the hypothesis that maximally activated detergent-treated (skinned) single fibers from normal and dystrophin-deficient dogs would incur comparable force deficits after stretch. Skinned cranial sartorius (CS) fibers from dystrophin-deficient and normal dogs were calcium-activated (pCa 4.5) and rapidly stretched. A single 30% stretch induced force deficits of 27.07 +/- 3.9% and 29.7 +/- 4.8% in dystrophin-deficient (n = 22) and normal (n = 18) fibers, respectively. Our data support the hypothesis that maximally activated skinned single fibers from normal and dystrophin-deficient dogs incur comparable force deficits after stretch. Our findings suggest that knowledge of the extent of stretch-induced force deficits following repeated stretch-activations in the GRMD dog may be useful to assess future therapeutic interventions aimed at replacing dystrophin in the sarcolemmal membrane.     

Laparoscopic management of suspicious adnexal masses

OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was >35 mIU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were >10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated. (Am J Obstet Gynecol 1996;175:1451-9.)     

Chronic activation of spinal adenosine A1 receptors results in hypersensitivity

Spinally administered adenosine reduces hypersensitivity in animals and humans with nerve injury, but also causes transient pain in humans and reduces tonic inhibition in spinal neurons. Nerve injury results in increased tonic spinal cord adenosine A1 receptor activation, consistent with a role for adenosine to generate hypersensitivity. Here, we demonstrate that chronic intrathecal adenosine induces hypersensitivity in normal animals and that chronic blockade of spinal adenosine A1 receptors by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine partially prevents nerve injury-induced hypersensitivity. In contrast, chronic blockade of spinal adenosine A1 receptors failed to reduce increased tonic G-protein signaling in the spinal cord after nerve injury. These data support a role for chronic adenosine A1 receptor stimulation after nerve injury to result in hypersensitivity.     

Fluorine-18-labeled tropane analogs for PET imaging studies of the dopamine transporter

A series of PET imaging studies were conducted with two fluorine-18-labeled tropane analoges, [(18)F](+)-FTT and [(18)F](+)-FCT. Both compounds possessed a high affinity and selectivity for the dopamine transporter and had a higher accumulation in the basal ganglia, a brain region having a high density of the dopamine transporter (DAT) than the cerebellum, a reference region devoid of dopaminergic terminals. [(18)F](+)-FCT had a higher brain uptake and more suitable basal ganglia:cerebellum (BG:Cb) ratio than [(18)F](+)-FTT. [(18)F](+)-FCT also displayed reversible binding kinetics in vivo, indicating that the measurement of DAT density in vivo with PET will be relatively insensitive to changes in cerebral blood flow that can occur as a consequence of disease or prolonged cocaine abuse. The uptake of [(18)F](+)-FCT was also displaced by an intravenous injection of cocaine (1.0 mg/kg), which is consistent with the labeling of the DAT in vivo by this radiotracer. These data suggest that [(18)F](+)-FCT may be a suitable radiotracer for studying DAT function in vivo with PET.     

An appraisal of "supernormal" A-V conduction

Certain temporal patterns of A-V and V-A transmission in experimental preparations resemble phenomena attributed to "supernormal" conduction in the clinic. Detailed study of the properties of the A-V transmission system in such experiments reveals alternative explanations in which supernormality is clearly eliminated. By application of similar principles, supernormality can be eliminated as a factor in most if not all of the published examples. Three major categories can be discerned: (1) occult 2:1 A-V block, in which an idioventricular beat "retracts" an otherwise refractory barrier within the A-V node; (2) alternation between dissociated intranodal transmission pathways; and (3) "ventriculophasic" (vagal) depression of nodal conductivity.     

UREAPLASMAS UREALYTICUM AND HUMAN INFERTILITY: EFFECT ON SPERMATOZOA MORPHOLOGY

Seminal fluids of 197 males with complaints of involuntary infertility were examined for spermatozoal counts, morphological changes in the spermatozoa and cultured for ureaplasmas and mycoplasmas. In 12, no spermatozoa were present, 29 had a count of less than one million and 156 had more than one million spermatozoa per mL of the seminal fluid. Various morphological changes were detected in the spermatozoa in some cases. U urealyticum and M hominis were grown in 43.15% and 16.75% in comparison to control figures of 15.9% and 11.4% respectively. There was no correlation between growth of ureaplasmas and the spermatozoal count. Among the morphological changes, presence of coiled tails, presence of a fuzzy coat around the tail and microcolonies were highly specific for culture positivity (98.2, 98.2 and 97.35% respectively) but of low sensitivity (55.2%, 14.1% and 8.2% respectively).KEY WORDS: Mycoplasma, Spermatozoa, Ureaplasma     

The contemporary appendectomy for acute uncomplicated appendicitis in children

BackgroundNational, procedure-specific clinical registries are increasingly available in surgery, although data about children have lagged behind. Data related to the surgical management of appendicitis in children have become available recently and can be used to inform patient and family expectations and to identify clinical areas in need of ongoing improvement.MethodsCases of acute, uncomplicated appendicitis in children (<18 years of age) were extracted from the 2017 pediatric appendectomy-targeted file of the American College of Surgeons National Surgical Quality Improvement Program. Epidemiologic data were generated across 5 domains: (1) patient characteristics/severity, (2) preoperative imaging patterns, (3) characteristics of the operation, (4) pathologic outcomes, and (5) postoperative morbidity and mortality.ResultsThe final sample included 9,507 appendectomies for acute, uncomplicated appendicitis performed at 106 hospitals. The population was predominantly male (60.6%), involving children 6 to 12 years of age (55.3%). Only 2.9% of patients did not have imaging before their appendectomy. Overall, 38.2% received a computed tomography; however, patients transferred with imaging received computed tomography at 3.8 times the rate of those with only local (ie, operating hospital) imaging. Laparoscopy was used in 94.6% of cases, with 1.1% converted to open. Negative appendectomy and complication rates were 3.3% and 2.1%, respectively. Children ≤5 years of age had 2.3 greater odds of negative appendectomy than children 6 to 17 years of age.ConclusionChildren undergoing operation for acute, uncomplicated appendicitis have excellent clinical outcomes, although children ≤5 years of age have an increased risk of negative appendectomy. Despite guidelines against their use, more than one-third of children received a computed tomography before operation, driven predominantly by transferring hospitals.