Inequalities in mortality of men by oral and pharyngeal cancer in Barcelona,Spain and São Paulo,Brazil, 1995–2003

Background  

Large inequalities of mortality by most cancers in general, by mouth and pharynx cancer in particular, have been associated to behaviour and geopolitical factors. The assessment of socioeconomic covariates of cancer mortality may be relevant to a full comprehension of distal determinants of the disease, and to appraise opportune interventions. The objective of this study was to compare socioeconomic inequalities in male mortality by oral and pharyngeal cancer in two major cities of Europe and South America.     

Influence of enteric citric acid on the release profile of 4-aminopyridine from HPMC matrix tablets

A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to study the influence of enteric citric acid (ECA) on the release profile from hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about gradual release of the drug. For this purpose, powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using first 900 ml HCl 0.1 N, and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf)=kt(n). As physically expected, increasing proportions (2-9%) of the in acid insoluble ECA decreased the release rate. In an acid medium, ECA acts as a physical barrier obstructing the diffusion path, dissolving after the pH change to 7.4. Both circumstances flattening the release profile. Apparent zero order release was observed at ECA concentrations of about 10%. The presence of ECA compensates the effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA proportions (10-50%) act increasing the dissolution rate. This is attributed to a void space formation around the insoluble ECA, after HPMC hydration, which percolates after a critical ECA proportion of approximately 10%. Moreover, decreasing release constant values (k) show a logarithmic relationship with increasing values of the exponent (n). This indicates that an apparent zero-order release can be obtained at a given release constant.     

Clinical impact of the detector size effect in 3D-CRT.

OBJECTIVE: The detector size artificially increases the measured penumbra of radiotherapy fields. The aim of this work is to determine the influence of the detector size when planning three-dimensional conformal radiation therapy (3D-CRT) treatments. MATERIAL AND METHODS: Two anatomical sites of interest in 3D-CRT were studied: prostate and hypophysis chordoma. Conventional 3D-CRT treatments for two cases in these locations were planned with a FOCUS 4.0.0 (Computerized Medical Systems, USA) treatment planning system (TPS) equipped with Fast Fourier Transform Convolution (FFTC) and Multigrid Superposition (MGS) algorithms, making use of beams modelled from radiation profiles measured either with a 2.0 mm diameter detector (PFD(3G) diode) or with a 5.5 mm diameter detector (PTW-31002 ionisation chamber). These detectors cover up the range of detector sizes commonly used to measure radiation profiles for 3D-CRT. Dose-volume histograms (DVHs), radiobiological indexes, tumor control probability (TCP) and normal tissue complication probability (NTCP) were analysed and compared for planning target volumes (PTVs) and organs at risk (OAR) studied. RESULTS: Important differences in DVH were found. OAR received higher dose levels when a 5.5 mm detector was used to measure profiles compared to the case in which a 2.0 mm detector was used. A 2 Gy increment in the mean rectal dose was found when the larger detector was used. In the same way, NTCP of brain stem in hypophysis chordoma treatments was doubled when this detector was used. CONCLUSION: The current use of ionisation chambers of about 5 mm active diameter to get the necessary data to model treatment machines in radiotherapy treatment planning systems (TPS) implies a significant overirradiation of OAR close to the PTV in 3D-CRT treatments due to errors in the measured penumbra of beam profiles. To avoid this overirradiation, the measured profiles should either being acquired with a suitable detector size (2-3 mm active diameter) or being deconvoluted.     

trans-4-[4-(Methoxyphenyl)cyclohexyl]-1-arylpiperazines: a new class of potent and selective 5-HT(1A) receptor ligands as conformationally constrained analogues of 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-arylpiperazines.

The present paper concerns the influence of conformational parameters on the recognition by rat 5-HT1A receptors of derivatives 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-(2-pyridinyl)piperazine (1a) and 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-N-[2-(2-pyridyloxy)ethyl]propanamine (3b), two highly potent and selective 5-HT1A receptor ligands. Fifteen corresponding flexible and rigid analogues were prepared following several synthetic routes and were tested in binding assays with radioligands at 5-HT1A, D2, and alpha1 receptors from rat brain membranes. Among the new derivatives emerged trans-4-[4-(3-methoxyphenyl)cyclohexyl]-1-(2-pyridinyl)piperazine (trans-8a) and trans-N-[4-(3-methoxyphenyl)cyclohexyl]-2-(2-pyridyloxy)ethylamine (trans-8b). These compounds can be considered as conformationally constrained analogues of compounds 1a and 3a, respectively. In fact, compounds trans-8a and trans-8b showed a marked enhancement in 5-HT1A receptor affinity when compared to the corresponding cis isomers. Because compound trans-8a was a potent and selective 5-HT1A ligand (K(i), nM: 5-HT1A = 0.028, D2 = 2194, alpha1 = 767), it was chosen as a lead to prepare other analogues that were tested at 5-HT1A, D2, and alpha1 receptors from rat brain membranes, showing high affinity at the 5-HT1A and selectivity vs D2 and alpha1 receptors. Selected compounds were tested for their affinity at the human cloned 5-HT1A, alpha1a, alpha1b, alpha1d receptor subtypes. They were also submitted to the [35S]GTPgammaS binding assay stimulating the 5-HT1A receptor-mediated G-protein activation, therefore behaving as full or as partial agonists. Finally, the ability of iv administration of trans-8a to induce fore-paw treading in rats was evaluated in comparison with 8-OH-DPAT. Although the affinity (K(i)) and in vitro activity (pD'2) of trans-8a at the 5-HT1A receptor were higher than those of 8-OH-DPAT, the compound was less potent than the reference standard in inducing the symptom.     

A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma

PURPOSE: To compare endoscopic cyclophotocoagulation (ECP) and the Ahmed drainage implant in the treatment of refractory glaucoma. METHODS: Sixty-eight eyes of 68 patients with refractory glaucoma were prospectively assigned to either ECP or Ahmed tube shunt implantation. All procedures were performed by a single surgeon. Eyes that were included were pseudophakic with a history of at least one trabeculectomy with antimetabolite, an intraocular pressure (IOP) equal to or above 35 mm Hg on maximum tolerated medical therapy, and a visual acuity better than light perception. Exclusion criteria included eyes that had had previous glaucoma drainage device implantation or a cyclodestructive procedure. Success was defined as an IOP more than 6 mm Hg and less than 21 mm Hg, with or without topical anti-hypertensive therapy. RESULTS: The mean follow-up was 19.82 +/- 8.35 months and 21.29 +/- 6.42 months, for the Ahmed and ECP groups, respectively (P = 0.4). The preoperative IOP, 41.32 +/- 3.03 mm Hg (Ahmed) and 41.61 +/- 3.42 mm Hg (ECP) (P = 0.5), and the mean postoperative IOP, at 24 months follow-up, 14.73 +/- 6.44 mm Hg (Ahmed) and 14.07 +/- 7.21 mm Hg (ECP) (P = 0.7), were significantly different from baseline in both groups (P < 0.001). Kaplan-Meier survival curve analysis showed a probability of success at 24 months of 70.59% and 73.53% for the Ahmed and ECP groups, respectively (P = 0.7). Complications included choroidal detachment (Ahmed 17.64%, ECP 2.94%), shallow anterior chamber (Ahmed 17.64%, ECP 0.0%), and hyphema (Ahmed 14.7%, ECP 17.64%). CONCLUSION: There was no difference in the success rate between the Ahmed Glaucoma Valve and ECP in refractory glaucoma. The eyes that underwent Ahmed tube shunt implantation had more complications than those treated with ECP.     

Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992–2003

Background  

The objective of this study was to assess trends in cancer mortality by educational level in Barcelona from 1992 to 2003.     

Maternal hyperthyroidism increases the prevalence of foregut atresias in fetal rats exposed to adriamycin

Purpose

Gastrointestinal malformations such as esophageal atresia with tracheoesophageal fistula (EA/TEF) and duodenal atresia (DA) have been reported in infants born to hyperthyroid mothers or with congenital hypothyroidism. The present study aimed to test whether maternal thyroid status during embryonic foregut division has any influence on the prevalence of EA/TEF and DA in an accepted rat model of these malformations.

Methods

Pregnant rats received either vehicle or 1.75 mg/kg i.p. adriamycin on gestational days 7, 8 and 9. Transient maternal hyper or hypothyroidism was induced by oral administration of levothyroxine (LT₄, 50 μg/kg/day) or propylthiouracil (PTU, 2 mg/kg/day), respectively, on days 7 to 12 of gestation. Plasma cholesterol, total T₃, free T₄ and TSH were measured at gestational days 7, 12, and 21. At the end of gestation, the mothers were sacrificed and embryo–fetal mortality was recorded. Fetuses were dissected to determine the prevalence of esophageal and intestinal atresias.

Results

At gestational day 12, mothers treated with LT₄ or PTU had hyper or hypothyroid status, respectively; plasma cholesterol levels were similar. In the adriamycin-exposed fetuses from hyperthyroid mothers, the embryonal resorption rate and the prevalence of both EA/TEF and DA were significantly higher than in the other groups; maternal hypothyroidism during the same period did not have significant effect on the prevalence of atresias.

Conclusions

Maternal hyperthyroidism during the embryonic window corresponding to foregut cleavage increased the prevalence of both EA/TEF and duodenal atresia in fetal rats exposed to adriamycin. This suggests that maternal thyroid hormone status might be involved in the pathogenesis of foregut atresias and invites further research on this likely clinically relevant issue in humans.     

Primary cutaneous diffuse large B-cell lymphoma of the leg according to the new WHO-EORTC classification. Two cases

Primary cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders characterized by skin involvement with no evidence of systemic disease at the time of diagnosis. Their clinical behavior is generally indolent, and only occasionally is the development of extracutaneous disease observed. Since the 1980s, primary cutaneous B-cell lymphomas have been considered a specific group of lymphomas, differentiated from both T-cell lymphomas and from secondary cutaneous B-cell lymphomas. Both the EORTC and the WHO have proposed alternative classifications for these entities, with significant discrepancies that were finally resolved through the development of a new classification (WHO-EORTC classification for cutaneous lymphomas), which standardizes criteria that had previously been different. We present two new cases of primary cutaneous diffuse large B-cell lymphoma of the leg according to the new classification.