Tramadol. Focus on musculoskeletal and neuropathic pain

In the light of the most recent acquisitions published in the international literature, this review analyzes the pharmacologic features and modes of use of tramadol, one of the most widely used, on a worldwide scale, analgesic agents in acute and chronic pain of moderate to severe intensity. The action of the 2 enantiomers of tramadol--which exert different pharmacologic effects--and of metabolite M1, is differentiated. The global activity of tramadol results from the sum of their specific actions. Data of kinetics show a very high oral bioavailability and the sustained-release (SR) formulations assure a 24-h coverage through the constant blood levels. Data reported in the relevant literature show that tramadol is effective in the treatment of arthrosic and neuropathic pain, with a value of Number Needed to Treat (NNT) of 3.4, and in the mixed nociceptive-neuropathic pain, especially in persistent or chronic pain. Moreover, tramadol maintains a good tolerability profile in the elderly subjects and a good analgesic efficacy in the long-term treatments with reduced pharmacological interactions and a low incidence of constipation. These global features assured its inclusion into the most recent guidelines on the management of chronic pain. Furthermore, data from literature showed that tramadol is devoid of immunosuppressive activity, has a poor tendency to tolerance and a minimum risk of addiction and abuse.     

Laparoscopic Gastric Bypass with Silicone Band in a Pig Model: Prevention of Anastomotic Dilatation – Feasibility Study

Background: Morbid obesity has become a major global health problem. Surgery remains the only effective treatment for patients with severe obesity, because diet reduction methods and pharmacologic agents have not resulted in long-term weight reduction. Gastric bypass (GBP) can provide adequate weight loss, but after some years, dilatation of the gastric pouch and outlet may lead to weight regain by allowing the patient to increase food intake. Methods: 2 groups of 6 pigs underwent laparoscopic GBP. In the first group, a non-adjustable silicone band (Proring?-band, IOC, Innovative Obesity Care, Saint Etienne, France) was positioned 1 cm proximal to the gastrojejunal anastomosis. In the second group, the device used to stabilize the gastric pouch was an adjustable silicone band (Mid-band?, Medical Innovation Developpement, Villeurbanne, France). Weight loss, complications and histological reaction were evaluated after 3 months. Results: Mortality rate was 25% (cardiac arrythmia in 2 pigs). Conversion rate was 25%. The positioning of the band was more difficult with the Mid-band? because of its larger size and the presence of the catheter. The average weight change in the Proring? group was 15.8 kg (3.5–25.1 kg), and in the Mid-band? group was 12.0 kg (6.2–15.1 kg). Morbidity consisted of one intragastric migration of the Proring? band into the gastrojejunal anastomosis, and one infection of the port in the Mid-band? group treated by removal of the port and antibiotics. Conclusion: Use of silicone devices may be safe and effective in the prevention of pouch or outlet dilatation after GBP.     

Oxycodone. Pharmacological profile and clinical data in chronic pain management

Opioids are widely used as effective analgesic therapy for cancer pain. Despite years of controversy, their use has been also accepted in chronic non-cancer pain. Oxycodone alone and in combination has been used for over 80 years in the treatment of a variety of pain syndromes. As single agent, the controlled release (CR) oxycodone's market in the USA grew from 10% in 1996 to 53% in 2000 and it has become a leading opioid in the United States. Recent data showed that the fixed-combination oxycodone/acetaminophen (5 mg/325 mg) is the most often prescribed opioid across all the different chronic pain diagnoses. Compared with morphine, oxycodone has a higher oral bioavailability and is about twice as potent. Pharmacokinetic-pharmacodynamic data support oxycodone as a pharmacologically active opiod that does not require conversion to oxymoprhone for pharmacological activity. Seven studies addressed the safety and efficacy of oxycodone for the treatment of non-cancer pain (low back pain, osteoarthritis pain, and painful diabetic neuropathy). Both immediate release (IR) and CR oxycodone are equally effective and safe. Along these trials, mean daily dosage of oxycodone was approximately 40 mg, with a low incidence of intolerable typical opiate side effects. In cancer pain, oxycodone can be considered a valid alternative to oral morphine to be used for opioid rotation. No difference in analgesic efficacy between CR oxycodone and CR morphine was found. Controlled-release preparations, with a long duration of action, are attractive because they offer the advantage of longer dosing intervals and sustained analgesic effect.     

Transient facial nerve paralysis after mandibular sagittal osteotomy

Facial nerve injuries are rare complications after orthognathic surgery. A literature review shows that such damages can develop with various mechanisms and are usually transient. Two cases of delayed facial paralysis after mandibular osteotomy with spontaneous recovery are reported.     

Persistent B-cell lymphopenia, multiorgan disease, and erythema multiforme caused by Mycoplasma pneumoniae infection

We report a 6-year-old girl in whom Mycoplasma pneumoniae infection presenting with erythema multiforme, multiorgan, and hematologic dysfunctions induced a long-standing, marked B-cell lymphopenia. An increase of CD8+ lymphocytes was also detected. We suggest that a selective cytotoxic T lymphocyte-dependent B cell lysis and the expansion of super-antigen activated CD8+ T cells may account for the multiorgan and hematologic disturbances triggered by M. pneumoniae.     

Suicide by buflomedil HCl: a case report

A man was found dead in his bed by his relatives; a half-empty wrapping of Loftyl Plus (the trade name of a vasodilator medications containing buflomedil HCl marketed in Italy) was on the bedside table. GC/MS analysis of a blood sample collected during the autopsy revealed a buflomedil HCl concentration approximately of about 20 times the therapeutic values.     

CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors

CDX-2 is a homeobox gene product essential for intestinal development and differentiation. It can be used as a specific marker of colorectal adenocarcinomas and other tumors with intestinal differentiation, but little is known about its expression in endocrine and neuroendocrine (NE) cells and NE primary and metastatic tumors. Using the Cdx-2-88 monoclonal antibody, we evaluated CDX-2 expression in routine samples of 20 normal endocrine/NE tissues and of 299 samples of well-differentiated NE tumors (WDNET) and high-grade NE carcinomas (NEC) from different sites. For 17 cases, we examined primary and corresponding metastatic lesions. We also examined 8 cytologic samples of liver metastases derived from 4 ileal WDNETs, 1 lung WDNET, and 3 pancreatic endocrine tumors. CDX-2 mRNA expression with RT-PCR technique on frozen material was evaluated in 5 WDNETs. CDX-2 was expressed in normal NE cells of the intestine and gastric fundus. High CDX-2 expression was seen in all ileal and appendiceal WDNET, while low levels were seen in WDNETs from stomach, duodenum, and rectum; no reactivity was seen in other WDNETs. Low levels of CDX-2 expression were seen in one third of nonfunctioning pancreatic WDNET where it was more frequently observed in cases with metastatic disease (P = 0.002). CDX-2 was identified in all cytologic specimens of metastatic ileal WDNETs. CDX-2 mRNA analysis confirmed immunohistochemical results. CDX-2 was expressed at high levels in 81% of intestinal NEC. Unexpectedly, variable levels of expression of CDX-2 were seen also in 39% of NEC of other sites, without any relation with the site of origin. This reactivity frequently overlapped TTF-1 expression, suggesting deregulated expression of homeobox genes in NEC. The restricted pattern of CDX-2 expression may have diagnostic value in the identification of the primary site of a metastatic WDNET. Conversely, a limited diagnostic role is suggested for CDX-2 in NEC because of its frequent expression in nongastrointestinal tumors.     

Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response that may contribute to clinical morbidity. Gaseous nitric oxide at relatively low concentrations may elicit peripheral anti-inflammatory effects in addition to a reduction of pulmonary resistances. We examined the effects of 20 ppm of inhaled nitric oxide administered for 8 hours during and after cardiopulmonary bypass. METHODS AND RESULTS: Twenty-nine consecutive patients undergoing aortic valve replacement combined with aortocoronary bypass were randomly allocated to either 20 ppm of inhaled nitric oxide (n = 14) or no additional inhalatory treatment (n = 15). Blood samples for total creatine kinase, creatine kinase MB fraction, and troponin I measurements were collected at 4, 12, 24, and 48 hours postsurgery. In addition, we collected perioperative blood samples for measurements of circulating nitric oxide by-products and brain natriuretic peptide. Soluble P-selectin was analyzed in blood samples withdrawn from the coronary sinus before and after aortic clamping. The area under the curve of creatine kinase MB fraction (P =.03), total creatine kinase (P =.04), and troponin I (P =.04) levels were significantly decreased in the nitric oxide-treated patients. Moreover, in the same group we observed blunted P-selectin and brain natriuretic peptide release (P =.01 and P =.02, respectively). Nitric oxide inhalation consistently enhanced nitric oxide metabolite levels (P =.01). CONCLUSIONS: Nitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties.     

Characterization of an aquaporin-2 water channel gene mutation causing partial nephrogenic diabetes insipidus in a Mexican family: evidence of increased frequency of the mutation in the town of origin

A Mexican family with partial congenital nephrogenic diabetes insipidus (NDI) that resulted from a mutation in the aquaporin-2 water channel (AQP2) was characterized, and the source of this rare mutation was traced to the family's town of origin in Mexico. Affected individuals with profound polyuria and polydipsia were homozygous for an autosomal recessive missense V168M mutation in the AQP2 gene. Expression in oocytes revealed that, although retained in the endoplasmic reticulum (ER) to a great extent, a considerable amount of the partially functional AQP2-V168M was expressed at the plasma membrane, and that its ER retention was less than AQP2-T126M, a functional mutant in severe recessive NDI. None of the affected AQP2-V168M individuals had neurologic deficits, which also suggested a milder form of the disease. The homozygous individuals reported subjective improvement in polyuria and polydipsia with the use of dDAVP (1-desamino-8-D-arginine-vasopressin). When clinically tested, infusion of dDAVP at variable doses produced a partial increase in the urinary osmolality in homozygous individuals and decreased their water intake. Heterozygotes were unaffected when compared with controls. Samples were obtained from the population of the Mexican town of origin of the family; 30% of the population was heterozygous for the V168M AQP2 mutation and 1% was homozygous for the mutation. The high frequency of this rare mutation in the town provides evidence for an important health care problem in the village with consequences for future generations.