Gabapentin for Cough in Cancer

Cough is a common problem among cancer patients, especially lung cancer patients. Gabapentin has been shown to be effective in reducing cough number and severity in patients with idiopathic refractory cough. The authors report here the successful use of gabapentin at usual doses to treat cough in cancer patients, including two with lung cancer, with minimal side effects. Gabapentin may be a useful addition to the symptom management toolbox for palliation of cancer symptoms.     

Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.     

Parathyroid pathology in an intrathyroidal position.

A systematic approach based on the embryology of the parathyroid glands should allow for the appropriate identification of both normal and abnormal glands at the time of parathyroidectomy. The exact role of subtotal thyroidectomy as part of this approach remains in question because of the low incidence of intrathyroidal adenomas reported in the past. From 1978 to 1992, 97 cervical explorations were performed in 96 patients (mean age: 56 years) with hyperparathyroidism. Four patients (4%) were found to have intrathyroidal parathyroid adenomas and were cured by ipsilateral partial or subtotal thyroid lobectomy on the side of a missing gland. One parathyroid adenoma completely replaced the right lobe of the thyroid, whereas two inferior and one superior intrathyroidal adenomas were found in the remaining three patients. The 4% incidence of intrathyroidal adenomas is higher than that reported in most series and suggests that this entity may be a more common cause of failed parathyroid explorations than is currently thought. Ipsilateral thyrotomy or subtotal thyroid lobectomy continues to be a potentially curative procedure for hyperparathyroidism when there is a missing and presumably diseased superior or inferior gland.     

New antinociceptive agents related to dihydrosphingosine

The main objective of this study was to evaluate the antinociceptive activity of three ethylenediamine derivatives and three β-aminoethanol lipidic derivatives structurally related to dihydrosphingosine. These derivatives were selected on the basis of previous results from in vitro and in vivo anti-inflammatory studies. For all of the assayed compounds, an intraperitoneal dose of 3 mg/kg caused pronounced pain inhibition as measured by the acetic acid-induced writhing model in mice. Compounds 3 and 6 demonstrated strong antinociceptive activity at doses as low as 1 mg/kg and proved to be considerably more potent than the common nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and acetaminophen (ACE). We further analyzed these compounds using the capsaicin- and glutamate-induced pain tests. Compounds 3 and 6 also exhibited considerable antinociceptive effects under these conditions, but their inhibitory effects in the formalin test were less pronounced. The exact mechanism of action for these compounds has yet to be established. However, based the results from a hot-plate test, it can be stated that these new drugs do not interact with the opioid system.     

Microcystin production by Radiocystis fernandoi (Chroococcales, Cyanobacteria) isolated from a drinking water reservoir in the city of Belém, PA, Brazilian Amazonia region.

During the monitoring of toxic cyanobacteria in the Utinga Reservoir, which is the main drinking water supply for the city of Belém, PA, Brazil, a Radiocystis fernandoi strain (SPC714) was isolated. This non-axenic strain was submitted to a toxicity bioassay with mice and microcystin production analyzed by HPLC-DAD. The species was identified based on cultured and natural preserved material. Morphometric, developmental and reproductive characteristics were analyzed. The strain was cultured in liquid ASM-1 medium, at 25+/-1 degrees C, at an incident irradiance of 20 micromol photon m(-2)s(-1) and constant aeration. At the end of the exponential growth phase, cells were lyophilized and submitted to toxicity tests. The strain showed high toxicity to mice, by intraperitoneal route, with an approximate LD100 of 60 mg kg(-1) of body weight, producing characteristic symptoms of hepatotoxicity. Analyses performed by HPLC-DAD confirmed the production of microcystins, in a concentration of 3.83 microg mg(-1) of lyophilized cells. This is the first reference related to the toxicity of the genus Radiocystis.     

TREK-1 channels do not mediate nitrergic neurotransmission in circular smooth muscle from the lower oesophageal sphincter

Background and purpose:

The ionic mechanisms underlying nitrergic inhibitory junction potentials (IJPs) in gut smooth muscle remain a matter of debate. Recently, it has been reported that opening of TWIK-related K⁺ channel 1 (TREK-1) K⁺ channels contributes to the nitrergic IJP in colonic smooth muscle. We investigated the effects of TREK-1 channel blockers on nitrergic neurotransmission in mouse and opossum lower oesophageal sphincter (LOS) circular smooth muscle (CSM).

Experimental approach:

The effects of TREK-1 channel blockers were characterized pharmacologically in murine and opossum gut smooth muscle using conventional intracellular and tension recordings.

Key results:

In LOS, L-methionine depolarized the resting membrane potential (RMP) but did not inhibit the nitrergic IJP. Cumulative application of theophylline hyperpolarized the RMP and inhibited the nitrergic IJP concentration dependently. The induced membrane hyperpolarization was prevented by pre-application of caffeine, but not by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. 8-Br-cAMP significantly hyperpolarized membrane potential and increased the amplitude of the nitrergic IJP. In opossum LOS muscle strips, L-methionine increased resting tone but had no effect on nerve-mediated LOS relaxation. On the other hand, theophylline markedly inhibited tone. In CSM from mouse proximal colon, L-methionine caused modest inhibition of nitrergic IJPs.

Conclusions and implications:

TREK-1 channels were not involved in the nitrergic IJP in LOS CSM. Not only does L-methionine have no effect on the nitrergic IJP or LOS relaxation, but the effect of theophylline appears to be due to interruption of Ca²⁺-releasing pathways (i.e. caffeine-like effect) rather than via blockade of TREK-1 channels.     

Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer.

Altered expression of cell cycle regulators represents a frequent event in both small cell and non-small cell lung cancer (NSCLC). Despite several studies that reported involvement of tumor suppressor genes, such as p53 and pRb, in the development and progression of lung cancer, contrasting opinions exist about the prognostic role of this protein in this neoplasm. We developed an immunohistochemical assay suitable for the detection of pRb2/p130, the last discovered member of the retinoblastoma gene family, on formalin-fixed and paraffin-embedded sections. We evaluated the immunohistochemical expression of pRb2/p130 in 135 lung cancer specimens, and performed Western blot analysis in a subset of 30 corresponding tumor lysates. A high correlation between immunohistochemical data and Western blot results (P = 0.0004) was found. We statistically analyzed the relationship between overall survival (OS) time and pRb2/p130 expression according to the different histological types in 105 patients. We did not find any correlation between pRb2/p130 expression and OS in small cell lung cancers, whereas in NSCLCs a direct relationship between pRb2 and OS was found in both adenocarcinoma (P = 0.0002) and squamous cell carcinoma (P = 0.0002) histotypes. According to univariate analysis, pRb2/p130 was a prognostic factor of which the lost or reduced expression correlated with a shorter OS (P < 0.0000). At multivariate analysis, pRb2/p130 expression was an independent predictor of OS (P = 0.0001) when considered together with histotype. This study demonstrates for the first time the potential independent prognostic value of pRb2/p130 expression on formalin-fixed, paraffin-embedded sections from lung cancer patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with NSCLC and, therefore, may represent a new prognostic marker.     

Controversial issues in vitiligo patients: a review of old and recent treatments

Vitiligo is quite a common hypopigmentary disorder, which may affect both children and adults with important psychological effects due to the well‐known leopard skin‐like appearance. The authors summarize in the present study the published evidence on vitiligo with particular interest on the controversial aspects of the disease, such as its definition and the available treatments.