Tapentadol prolonged release in association with analgesic radiofrequency for the treatment of chronic lumbar radicular pain: an observational, prospective study.

OBJECTIVE: Chronic pain is frequently irreversible, representing a major health problem. A survey has shown that 19% of European adults experience chronic pain which is not adequately managed. Innovative interventional techniques for the treatment of chronic pain have been developed, as a further step beyond the three-layer WHO analgesic ladder. Among these techniques, continuous and pulsed radiofrequency (RF) are very effective in the management of radicular pain syndrome. Usually, these techniques are associated with a pharmacologic approach with a wide-spectrum analgesic. Tapentadol has a double mechanism of action, as a µ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibitor (NRI), contributing synergistically to its analgesic efficacy on both nociceptive and neuropathic pain. PATIENTS AND METHODS: We aimed to test the efficacy of tapentadol prolonged release (PR) combined with pulsed RF in improving neuropathic symptoms and disability in 50 patients with moderate-to-severe chronic pain due to lumbar radiculopathy. RESULTS: The responders to treatment, showing at least a 30% reduction in pain intensity on the Numerical Rating Scale (NRS), were 38 (76%). Both average NRS at rest and during loading were statistically significantly reduced compared with baseline (p<0.0001). Other parameters investigated (sleep quality, neuropathic symptoms, the degree of disability) were all statistically better with tapentadol PR. Patients requiring RF intervention dropped dramatically from 98% at baseline to 10% at the end of the study (p<0.01). Adverse events were reported in 14 patients (28%), four of which required therapy discontinuation. However, patients' satisfaction and overall tolerability of tapentadol PR treatment were high. CONCLUSIONS: Tapentadol PR is effective in reducing pain intensity at rest and during loading, with a favorable safety and tolerability profile. Moreover, the use of tapentadol PR decreases the degree and severity of disability, as well as the intensity of neuropathic symptoms.

Tetraplegia and respiratory failure following mild cervical trauma in a child with Cornelia De Lange syndrome.

Here we report a 6-year-old female patient with Cornelia de Lange syndrome who developed tetraplegia and respiratory failure after a seemingly trivial spinal trauma due to an spinal malformation that has not yet been described.

Release of aldosterone and catecholamines from the interrenal gland of Triturus carnifex in response to adrenocorticotropic hormone (ACTH) administration.

The influence of adrenocorticotropic hormone (ACTH) on the interrenal gland of Triturus carnifex was investigated by in vivo administration of synthetic ACTH. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the circulating serum levels of aldosterone, noradrenaline (NA), and adrenaline (A). In June and November, ACTH administration increased aldosterone release (from 281.50 +/- 1.60 pg/ml in carrier-injected newts to 597.02 +/- 3.35 pg/ml in June; from 187.45 +/- 1.34 pg/ml in carrier-injected animals to 651.00 +/- 3.61 pg/ml in November). The steroidogenic cells showed clear signs of stimulation, together with a reduction of lipid content in June and an increase of lipid content in November. Moreover, ACTH administration decreased the mean total number of secretory vesicles in the chromaffin cells in June (from 7.73 +/- 0.60 granules/microm2 in carrier-injected animals to 5.91 +/- 0.40 granules/microm2) and November (from 7.78 +/- 0.75 granules/microm2 in carrier-injected newts to 4.87 +/- 0.40 granules/microm2). In June, however, when T. carnifex chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm2; A: 0.32 +/- 0.13 granules/microm2), ACTH decreased NA content (5.52 +/- 0.32 granules/microm2) increasing NA release (from 639.82 +/- 3.30 pg/ml in carrier-injected to 880.55 +/- 4.52 pg/ml). In November, when both catecholamines, NA (3.92 +/- 0.34 granules/microm2) and A (3.84 +/- 0.33 granules/microm2), are present in the chromaffin cells, ACTH administration reduced A content (1.02 +/- 0.20 granules/microm2), enhancing adrenaline secretion (from 681.30 +/- 3.62 pg/ml in carrier-injected newts to 1,335.73 +/- 9.03 pg/ml). The results of this study indicate that ACTH influences the steroidogenic tissue, eliciting aldosterone release. The effects on the chromaffin tissue, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the increase of aldosterone release. Finally, the lack of an increase of A content in the chromaffin cells, or A serum level, following ACTH administration in June might suggest an independence of PNMT enzyme on corticosteroids.

Annual variations of adrenal gland hormones in the lizard Podarcis sicula.

The adrenal gland regulates metabolism and maintains normal electrolyte balance. Adrenal hormones are equivalent in all vertebrates; the chromaffin tissue produces adrenaline and noradrenaline and the steroidogenic tissue produces most of the steroid hormones present in mammals. Podarcis sicula belongs to the Squamata family of lizards and it is the most abundant lizard species in southern Italy. This species shows a reproductive annual cycle and the presence of seasonal variations in the activity of the hypothalamus-hypophyseal-thyroid axis. To investigate the existence of an annual cycle of lizard adrenal gland, we have measured plasma concentrations of corticosterone, ACTH, noradrenaline and adrenaline. We have shown that corticosterone rapidly increased from January to March to reach a peak value that persisted until July, then, it slowly decreased until December. ACTH levels increased from January to May and slowly decreased from July to December. Noradrenaline levels were higher in March and then decreased until December. On the contrary, adrenaline levels increased from March to July and slowly decreased until December. Our results demonstrate the existence of an annual cycle of the lizard adrenal gland activity. This is very interesting because its activity is important to rightly regulate the reproductive status of the Podarcis sicula lizard.

Effects of adrenaline administration on the interrenal gland of the newt, Triturus carnifex: evidence of intraadrenal paracrine interactions.

The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo adrenaline (A) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, noradrenaline (NA), and adrenaline. In March and July, adrenaline administration reduced aldosterone release (from 187.23 +/- 2.93 pg/ml to 32.28 +/- 1.85 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 87.51 +/- 2.57 pg/ml in July) from steroidogenic cells. The cells showed clear signs of lowered activity: they appeared full of lipid, forming large droplets. Moreover, adrenaline administration decreased the mean total number of secretory granules in the chromaffin cells in July (from 7.74 +/- 0.74 granules/microm(2) to 5.14 +/- 1.55 granules/microm(2)). In this period T. carnifex chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm(2); A: 0.32 +/- 0.13 granules/microm(2)). Adrenaline administration reduced noradrenaline content (4.36 +/- 1.40 granules/microm(2)) in the chromaffin cells, enhancing noradrenaline secretion (from 640.19 +/- 1.65 pg/ml to 1030.16 +/- 3.03 pg/ml). In March, adrenaline administration did not affect the mean total number of secretory vesicles (from 7.24 +/- 0.18 granules/microm(2) to 7.25 +/- 1.97 granules/microm(2)). In this period the chromaffin cells contain both catecholamines, noradrenaline (3.88 +/- 0.13 granules/microm(2)), and adrenaline (3.36 +/- 0.05 granules/microm(2)), in almost equal quantities; adrenaline administration reduced adrenaline content (1.74 +/- 0.84 granules/microm(2)), increasing adrenaline release (from 681.27 +/- 1.83 pg/ml to 951.77 +/- 4.11 pg/ml). The results of this study indicate that adrenaline influences the steroidogenic cells, inhibiting aldosterone release. Adrenaline effects on the chromaffin cells (increase of noradrenaline or adrenaline secretion) vary according to the period of chromaffin cell functional cycle. The existence of intraadrenal paracrine interactions in T. carnifex is discussed.

Effects of noradrenaline administration on the interrenal gland of the newt, Triturus carnifex: evidence of intra-adrenal paracrine interactions.

The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo noradrenaline (NA) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, NA, and adrenaline (A). In March and July, NA administration increased aldosterone release (from 187.23 +/- 2.93 pg/ml to 878.31 +/- 6.13 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 622.51 +/- 2.65 pg/ml in July) from steroidogenic cells. The cells showed clear signs of stimulation, as evidenced by a strong reduction of lipid content. Moreover, NA administration decreased the mean total number of secretory vesicles in the chromaffin cells in March (from 7.24 +/- 0.18 granules/micro2 to 5.57 +/- 1.88 granules/micro2) and July (from 7.74 +/- 0.74 granules/micro2 to 6.04 +/- 1.13 granules/micro2). In March, however, when T. carnifex chromaffin cells contain both catecholamines, NA (3.88 +/- 0.13 granules/micro2) and A (3.36 +/- 0.05 granules/micro2) in almost equal quantities, NA administration reduced A content (1.29 +/- 1.04 granules/micro2) in the chromaffin cells, enhancing adrenaline secretion (from 681.27 +/- 1.83 pg/ml to 1527.02 +/- 2.11 pg/ml). In July, when the chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/micro2; A: 0.32 +/- 0.13 granules/micro2), NA administration reduced the number of NA granules (5.45 +/- 1.10 granules/micro2), thereby increasing noradrenaline release from the chromaffin cells (from 640.19 +/- 1.65 pg/ml to 1217.0 +/- 1.14 pg/ml). The results of this study indicate that NA influences the steroidogenic cells, eliciting aldosterone release. Noradrenalin effects on the chromaffin cells, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the steroidogenic cells. The existence of intra-adrenal paracrine interactions in T. carnifex is discussed.

Immunocytochemical localization of substance P in the adrenal gland of Podarcis sicula (Reptilia, Lacertidae): evidence for its involvement in the modulation of adrenal activity.

The occurrence of substance P (SP) immunoreactivity was investigated in the adrenal gland of the lizard Podarcis sicula by ABC immunocytochemical technique: SP-immunoreactivity was present in both adrenaline and noradrenaline cells, in ganglion cells and nerve fibers in the connective capsule surrounding the gland. The involvement of substance P in the modulation of pituitary-interrenal axis was studied in vivo by intraperitoneal injections of SP. The effects were estimated by means of the morphological and morphometrical features of the tissues, as well as the plasma levels of adrenocorticotropic hormone (ACTH), corticosterone and catecholamines, adrenaline and noradrenaline. Substance P (0.07 mg/100 g body wt) decreased ACTH plasma levels and raised corticosterone release from steroidogenic tissue, that showed clear signs of stimulation. In the chromaffin tissue, the decrease in the number of noradrenaline cells, and the increase in the number of adrenaline cells, lowered numeric noradrenaline/adrenaline cell ratio. Moreover, an increase in adrenaline plasma level and a decrease in noradrenaline plasma level were found. The results suggest that (1) also in Reptiles as in other Vertebrates, SP may affect pituitary-adrenal axis activity, and (2) the chromaffin cells may be involved in the paracrine control of steroidogenic activity.

Shift from noradrenaline to adrenaline production in the adrenal gland of the lizard, Podarcis sicula, after stimulation with vasoactive intestinal peptide (VIP).

The aim of this study was to investigate the distribution and function of VIP in the adrenal gland of the lizard, Podarcis sicula. We have shown by immunohistochemistry that VIP fibers were localized exclusively around clusters of chromaffin cells in the dorsal ribbon of the lizard adrenal gland. Moreover, a strong positivity for this peptide was observed within ganglial cells and within most chromaffin cells of the gland. To investigate the effects of VIP on the adrenal gland, we have treated lizards with several doses of this peptide and we have shown that injections of exogenous VIP increased plasma levels of catecholamines and corticosteroids, but not of ACTH. This probably suggests a direct effect of VIP on the control of adrenal hormone secretion without the involvement of the hypothalamo-hypophyseal axis. Our results also establish that the increased levels of the hormones were modulated in a time- and dose-dependent manner. Therefore, our morphological studies showed a clear increased function of steroidogenic cells. In the medullary region, VIP administration induced not only a functional enhancement of adrenaline release from adrenergic cells, but also a shift of noradrenaline cells to adrenaline ones.

Immunohistochemical localization of NPY, VIP and 5-HT in the thyroid gland of the lizard, Podarcis sicula.

The thyroid gland of the lizard Podarcis sicula was immunohistochemically studied in adult male specimens using specific antibodies against NPY, VIP and 5-HT and the avidin-biotin peroxidase complex (ABC) procedure to localize the three peptides. Fine beaded VIP-immunoreactive nerve fibers ran between the follicles, and VIP-immunoreactivity was evenly distributed in the apical cytoplasm of follicular cells. NPY-immunoreactive fibers were found around the follicles, and, in the cells, immunoreactivity was localizated only in the cellular apices. Immunoreactivity to 5-HT was observed in the colloid, with a concentration in the follicular lumen exceeding that in the follicular cells. In fact, most follicles showed immunoreactivity in the cytoplasmic bridges formed between the apical portion of the follicular cells and the colloid.

Inhibin in the testis and adrenal gland of the male lacertid, Podarcis sicula Raf.: a light immunocytochemical study.

Inhibin is a glycoproteic hormone mostly produced by the gonads. Through a feedback at the pituitary level, it selectively inhibits the release of follicle-stimulating hormone. In mammals, inhibin has been found also in some extragonadal tissues such as placenta, pituitary, adrenal, spleen, kidney, brain and spinal cord. At present, no information is available about the existence of inhibin in reptiles. The aim of the present work is to localise, through immunocytochemical methods, the sites of inhibin production in male lizards during the main phases of the reproductive cycle: the culmination phase (April-June), the early regressive phase (early July), the maximal regressive phase (August) and the winter stasis (January). In the testis, immunostaining is mainly localised in the Leydig cells during the early regressive phase, while it is observed in the Sertoli cells during the maximal regressive phase. In the epididymis, the immunostaining is present only during the reproductive period at the level of secreting cells and inside its ducts. In the adrenal gland, after immunostaining, both chromaffin and steroidogenetic tissues are inhibin-positive during the whole spermatogenetic cycle, though with variable intensity throughout the year: cross-reaction appears more evident from January to April (winter stasis and culmination phase) and weaker in June. However, in captive animals, the reaction persists in chromaffin cells, but disappears in steroidogenetic cells. The functional meaning of the presence of inhibin as a factor in the local regulation of spermatogenesis is discussed.

An immunocytochemical study of the endocrine pancreas in three genera of lacertids.

The comparative morphology of the endocrine pancreas was studied in 11 species of lacertids. Four major cell types were identified immunocytochemically in the endocrine pancreas: glucagon-immunoreactive A-cells, insulin-immunoreactive B-cells, somatostatin-(SRIF)-immunoreactive D-cells, and pancreatic polypeptide(PP)-immunoreactive F-cells. Different distributions of the four cell types were seen in the endocrine tissue within the exocrine parenchyma. F-cells were rare or absent in the splenic lobe and abundant in the duodenal lobe, in which they were usually widespread in the exocrine parenchyma and rarer in the islets. The other three cell types were always present in the islets. The central core consisted of B- and A-cells, with B-cells predominating. The peripheral mantle was formed by A-cells and less abundant D-cells. Rare D-cells were also found in the central core. D- and F-cells showed projections often closely associated with capillaries. The observed arrangements in islets and isolated cells may represent an endocrine network that, in addition to systemic actions, may regulate exocrine function in a paracrine fashion.

Endocrinologic effects of the anaesthetic propofol.

Because of the similarities of the adrenal glands of mammals and of the lizard Podarcis s. sicula, the latter has already been the subject of various studies on the effects of Propofol and other anaesthetics. Because a relationship between the activities of the thyroid and adrenal glands of this species has been demonstrated, the authors administered Propofol to a species of lizard to investigate its effects on the thyroid gland. Propofol inhibited thyroid activity, promoted steroid synthesis, and caused the contemporaneous appearance of both adrenaline and noradrenaline granules in the cytoplasm of the chromaffin cells. These results suggest that inhibition of the activity of the thyroid gland is secondary to the action of Propofol on the adrenal gland.

The endocrine pancreas of Podarcis s. sicula Raf.: an immunocytochemical study at light and electron microscopic levels.

The endocrine pancreas of Podarcis s. sicula Raf. was investigated at light and electron microscopic levels using immunocytochemical methods. It was constituted by endocrine islets, which were concentrated more in the splenic than in the duodenal region, and never formed large clusters. At the light and electron microscope, with the peroxidase-antiperoxidase reaction (PAP) and the colloidal gold technique, four cell types were identified: glucagon-positive A-cells, insulin-positive B-cells, somatostatin-positive D-cells and pancreatic polypeptide-positive F- or PP-cells. F- or PP-cells showed a different regional distribution, being absent or very rare in the splenic lobe of the pancreas and numerous in the duodenal lobe, where they were seldom found in the islets, but were scattered in the exocrine parenchyma. The functional meaning of F-cells is discussed. The E.M. observations were carried out at the CIRUB (Centro Interdipartimentale di Ricerca sulle Ultrastrutture Biologiche) of the University of Naples.

The endocrine pancreas of Triturus cristatus: an immunocytochemical study.

The endocrine pancreas of Triturus cristatus carnifex was studied with the aid of immunocytochemical methods, showing cells immunoreactive to anti-insulin serum (B cells), a small population of cells immunoreactive to anti-glucagon serum only (A cells), rare cells positive to anti-PP serum only (PP or F cells), and a larger population of cells immunoreactive both to anti-glucagon and to anti-PP sera. B cells lied in the core of the islet, while the A/PP cells were located at the periphery, forming digitations extending into the exocrine parenchyma. D cells were present in small number in the islet while they were more numerous scattered in the exocrine parenchyma. A/PP cells as well as D cells showed one or two long cytoplasmic extensions often in contact with blood vessels.

Pharyngeal size and resistance in obstructive sleep apnea.

Although anatomic and physiologic abnormalities of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea (OSA), the relative contributions of these factors have not been elucidated. We therefore measured pharyngeal cross-sectional area (PCSA) and pharyngeal air-flow resistance (Rp) in 12 overweight men with severe symptomatic OSA (mean apnea plus hypopnea index [AHI], 66.9 +/- 6.0 events per hour) and in 17 age- and weight-matched control subjects without spontaneous complaints of OSA symptoms (mean AHI, 4.9 +/- 1.6 events per hour). During wakefulness, PCSA was assessed during breath cessation at FRC by computed tomography (CT) and Rp by measuring inspiratory air-flow resistance between the choanae and epiglottis. No measure of PCSA differed significantly between patients and control subjects, and only 1 measure of PCSA, minimal pharyngeal area, correlated with AHI in all subjects (r = -0.38, p less than 0.05). In contrast, Rp was significantly higher (p less than 0.05) in patients (6.9 +/- 1.0 cm H2O/L/s) than in all control subjects (4.2 +/- 0.5 cm H2O/L/s) and correlated significantly with AHI (r = 0.53, p less than 0.01). We conclude that increased inspiratory resistance to air flow in the naso-oropharynx is present during wakefulness in overweight men with OSA, when compared with matched control subjects without symptomatic OSA, and is associated with disordered breathing during sleep. This occurs even though computed tomography is unable to demonstrate that pharyngeal size during wakefulness at FRC is significantly different between patients and control subjects. These observations suggest that the ability to dilate the pharynx during inspiration may be defective in patients with OSA.

Assessment of the risk of vertebral fracture in menopausal women.

The decision to institute prophylaxis in women with menopausal osteopenia is hampered by the absence of quantitative criteria for appraising the risk of fracture in the individual. We have developed standards for assessing the risk of fracture by relating the prevalence of atraumatic vertebral compression fractures to bone density in sixty-five menopausal women, forty-nine to ninety-two years old. To define the upper limit of the spectrum of bone density, we also studied thirty-one young women, seventeen to twenty-two years old. The density of trabecular bone in a vertebral body was determined by quantitative computed tomography and expressed in terms of milligrams per milliliter of dipotassium hydrogen phosphate. Twenty-five of the menopausal women exhibited at least one fracture (range, one to six fractures), and forty had no fracture. The bone density ranged from -9 to sixty-nine milligrams per milliliter in those with fractures and from twelve to 122 milligrams per milliliter in those without a fracture. The densities in the young women averaged 173 milligrams per milliliter and ranged from ninety-five to 248 milligrams per milliliter. The percentage of subjects with fractures increased as the bone density decreased. It was zero per cent in women with a density of seventy milligrams per milliliter or more, 38 per cent in women with a density between fifty and less than seventy milligrams per milliliter, 71 per cent in those with a density between thirty and less than fifty milligrams per milliliter, and 82 per cent in women with a density of less than thirty milligrams per milliliter.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of testosterone on breathing during sleep.

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.

Effects of ketamine on the catecholamine containing cells of the adrenal gland of the lizard Podarcis s. sicula Raf.

The authors studied the effects of ketamine on the morphology of the adrenal gland of Podarcis s. sicula Raf.. Low doses of the drug failed to anesthetize the lizards and did not cause significant changes in the morphology of the adrenal cells. Higher doses of ketamine caused deep anesthesia and marked depletion of catecholamine granules. The results support the theory that ketamine acts on the peripheral autonomic nervous system and sympathetic ganglia.

Cochlear aqueduct radiographic anatomy in temporal bone preparations and in sudden hearing loss.

Sudden sensorineural hearing loss appears to have many possible etiologic factors. Shea has presented work indicating that a large cochlear aqueduct (CA) is frequently present on the side of an idiopathic sudden sensorineural hearing loss (ISHL). However, Valvassori, on performing temporal bone tomographic studies on several hundred patients complaining of ISHL, has not found enlargement of the CA in a statistically significant number of these cases. In an attempt to resolve this discrepancy, a single blind study was performed utilizing temporal bone polytomography to evaluate the presence or absence of the CA in 22 adult patients. One-half of these patients had a history of ISHL, while the remaining patients had other complaints as an indication for tomography. In all cases, the CA was identified. The CA was felt to be enlarged in 1 patient suffering from ISHL, in the nonaffected ear of 1 patient with unilateral ISHL, and in 2 control patients. There was, therefore, no positive correlation between CA enlargement and the occurrence of ISHL. In order to further elucidate the radiologic anatomy of the CA, 9 pairs of adult temporal bones removed at autopsy were studied by polytomography after cannulation and injection of radiopaque material. Measurements of the dimensions of the CA and its radiographic anatomy are discussed and compared to measurements obtained from histopathologic evaluation of the temporal bone.