Study of the association of bladder cancer and phenacetin use. Problems set by a pharmaco-epidemiological study]

In a survey of the literature, phenacetin appears to be responsible for an increased risk of urothelial tumours in humans, especially renal pelvis tumour. Few observations have suggested an association between bladder cancer and phenacetin containing analgesics however. To assess this association in France, a case-control study of bladder cancer (143 cases, 120 controls) was undertaken. We point at some methodological difficulties, such as difficulties of recall, definition of a control group, non-responses, possible French distinctive features of analgesics use. Results are not able to confirm the suspected relationship between bladder cancer and phenacetin use.     

Contralateral haemorrhagic pulmonary metastases (“choriocarcinoma syndrome”) after pneumonectomy for primary pulmonary choriocarcinoma

The case history is presented of a patient which illustrates both the diagnostic difficulties of an extremely rare tumour (choriocarcinoma of the lung) and its associated haemorrhagic metastases (“choriocarcinoma syndrome”).     

Parental occupation, occupational exposure to solvents and polycyclic aromatic hydrocarbons and risk of childhood brain tumors (Italy, France, Spain)

The role of parental occupational exposure in childhood brain tumorswas investigated in a population-based case-control study grouping 251 casesand 601 controls from three European centers: Milan (Italy), Paris (France),and Valencia (Spain). Parental occupational exposure to solvents andpolycyclic aromatic hydrocarbons (PAH) during the five-year period beforebirth was estimated using a job-exposure matrix developed earlier in the samecountries. Odds ratios (OR) of brain tumors for each occupation andoccupational exposure were estimated by logistic regression, adjusting forchilds age, gender, exposure to tobacco smoke and ionizing radiation,mothers age and years of schooling, and center. The risk of childhood braintumors rose when fathers worked in agriculture (OR = 2.2, 95 percentconfidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. Inthe latter group, the risk increased for primitive neuroectodermal tumors inparticular (OR = 2.7, CI = 1.1-6. 6). Astroglial tumors were more frequentamong children of mothers in health services (OR = 2.2, CI = 1.0-4.9).Paternal exposure to PAHs was associated with an increased, but notdose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI =1.0-4.0), and maternal exposure to solvents at a high level was associatedwith an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) andprimitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3).     

Endothelins Inhibit Junctional Permeability in Cultured Mouse Astrocytes

Endothelins, a family of potent vasoconstrictor peptides initially characterized in peripheral tissues, have also been reported to be synthesized in the brain. In this structure several cell types, including astrocytes, endothelial cells and certain neurons, are potential targets for these peptides. In astrocytes, endothelins induce changes in the concentration of several second messengers (calcium, diacylglycerol, arachidonic acid, cAMP) known to be involved in the regulation of gap junction channels. Using the scrape loading/dye transfer technique we have observed that two isoforms of endothelin, endothelin-1 and endothelin-3, strongly inhibit the extent of dye-coupling between confluent astrocytes, suggesting that gap junction permeability was reduced. This inhibitory effect on dye coupling was reproduced by the snake venom sarafotoxin. When used at 10⁻⁷ M, these three compounds had inhibitory effects on gap junction channels which were comparable to those induced by the well known uncoupling agents octanol and halothane. In the absence of extracellular calcium, the effects of endothelins were largely prevented, suggesting that second messengers linked to the activation of phospholipases C and/or A₂, which both are dependent on external calcium, could be involved in the uncoupling mechanism.     

Synergistic Regulation of Cytosolic Ca2+ Concentration by Adenosine and alpha1-Adrenergic Agonists in Mouse Striatal Astrocytes

Adenosine has a broad array of actions on neurons but astrocytes also possess adenosine receptors. We have previously shown that adenosine, by acting on astrocytes in the striatum, can modulate neuronal responses mediated by receptors coupled to phospholipase C through an astrocyto - neuronal interaction. In addition, adenosine was found to potentiate the alpha1-adrenergic production of inositol phosphates in astrocytes. The mechanism involved in this potentiation was further investigated by examining the effects of adenosine and alpha1-adrenergic receptor agonists on cytosolic Ca2+ in cultured striatal astrocytes from the embryonic mouse in primary culture. When used alone, methoxamine, a selective agonist of alpha-adrenergic receptors or 2-chloroadenosine, a stable analogue of adenosine, induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+, which seems to be due to a Ca2+ influx, because it was not observed in the absence of external Ca2+. Voltage independent Ca2+ channels contribute to this process and different blockers of voltage-operated calcium channels, such as dihydropyridines, phenylalkylamines, La3+ or Co2+ were ineffective in suppressing the sustained cytosolic Ca2+ elevation. Three observations suggest the implication of arachidonic acid in the observed potentiation: (i) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the coapplication of methoxamine and 2-chloroadenosine; (ii) the addition of arachidonic acid during the calcic plateau produced by the combined application of the agonists did not increase further cytosolic Ca2+ levels; (iii) in the presence of methoxamine, 2-chloroadenosine induced a release of arachidonic acid. The stimulation of phospholipase C and the resulting activation of protein kinase C induced by methoxamine seem to be required for the potentiating effect of 2-chloroadenosine on cytosolic Ca2+. In fact, the direct activation of protein kinase C by an exogenous diacylglycerol analogue mimicked the effect of methoxamine because, in this condition, 2-chloroadenosine alone evoked a sustained elevation of cytosolic Ca2+. Therefore, methoxamine, through the successive activation of phospholipase C and protein kinase C, could allow a lipase, probably phospholipase A2, to be stimulated by 2-chloroadenosine. Arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates in other cell types. Therefore, in striatal astrocytes, 2-chloroadenosine, through an arachidonic acid-mediated hyperpolarization, could increase the Ca2+ driving force and thus improve Ca2+ influx through inositol phosphate-gated channels. This hypothesis is further supported by the suppressing effect of a 50 mM KCI-induced depolarization on the long lasting elevation of cytosolic Ca2+ seen in the combined presence of 2-chloroadenosine and methoxamine.     

Treatment of External Auditory Canal Exostoses

Exostoses of the external auditory canal can occur in patients living in coastal, southern California communities with a history of cold-water aquatic activities such as ocean surfing and swimming. Although most canal exostoses are asymptomatic, patients with canal obstruction greater than 80% can have recurrent episodes of external otitis and a related conductive hearing loss. In most cases, medical treatment resolves the symptomatic external otitis and related hearing loss. Patients recalcitrant to medical treatment are candidates for surgical removal of the exostoses. This report reviews the authors' surgical experience with 18 patients (27 ears) who have undergone surgical removal of exostoses. Their preferred surgical technique of transmeatal removal of exostoses with a specialized mallet and thin chisel under local anesthesia is described.     

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis.

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.