The carcinogenicity of environmental tobacco smoke

Male strain A/J mice were exposed for 6 h a day, 5 days a week to environmental tobacco smoke (ETS) generated from Kentucky 1R4F reference cigarettes. Chamber concentrations were 87 mg/m3 of total suspended particulate matter (TSP), 246 p.p.m. of CO and 16 mg/m3 of nicotine. After 5 months, 33% of the ETS exposed and 11% of the control animals had one or several lung tumors; the difference was statistically not significant. A second group of animals exposed for 5 months to ETS was allowed to recover for another 4 months in filtered air. When they were killed, 85% of the ETS animals had lung tumors (average number per lung: 1.4 +/- 0.2), whereas in the control group 38% had lung tumors (average number of lung tumors in all animals 0.5 +/- 0.2). The differences in tumor incidence and multiplicity were statistically significant. More than 80% of all tumors were adenomas, the rest adenocarcinomas. When animals were pretreated with a carcinogen, lung tumor multiplicity was lower in the ETS exposed animals after 5 months compared with controls injected with a carcinogen and kept in air. However, after an additional 4 month recovery period in air, lung tumor multiplicities were the same in ETS plus carcinogen exposed mice as in carcinogen-treated air-exposed controls. Histopathologic and morphometric analysis of the lung tissue failed to reveal any differences between ETS exposed and control animals. However, immediately after ETS exposure, immunohistochemistry revealed increased staining for CYP1A1 in airway epithelia and lung parenchyma; following recovery in air, the staining disappeared again. Analysis of cell kinetics showed an initial burst of increased DNA synthesis in the epithelial cells of the airways and a smaller early positive response in the parenchyma. Feeding of butylated hydroxytoluene during ETS exposure did not modulate lung tumor development. It was concluded that ETS is a pulmonary carcinogen in strain A/J mice.     

Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.     

Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care

Multidisciplinary team (MDT) meetings are becoming the model of care for cancer patients worldwide. While MDTs have improved the quality of cancer care, the meetings impose substantial time pressure on the members, who generally attend several such MDTs. We describe Lung Cancer Assistant (LCA), a clinical decision support (CDS) prototype designed to assist the experts in the treatment selection decisions in the lung cancer MDTs. A novel feature of LCA is its ability to provide rule-based and probabilistic decision support within a single platform. The guideline-based CDS is based on clinical guideline rules, while the probabilistic CDS is based on a Bayesian network trained on the English Lung Cancer Audit Database (LUCADA). We assess rule-based and probabilistic recommendations based on their concordances with the treatments recorded in LUCADA. Our results reveal that the guideline rule-based recommendations perform well in simulating the recorded treatments with exact and partial concordance rates of 0.57 and 0.79, respectively. On the other hand, the exact and partial concordance rates achieved with probabilistic results are relatively poorer with 0.27 and 0.76. However, probabilistic decision support fulfils a complementary role in providing accurate survival estimations. Compared to recorded treatments, both CDS approaches promote higher resection rates and multimodality treatments.     

Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis, and heparin activation

The inherent variability of conformational diseases is demonstrated by two families with different mutations of the same conserved aminoacid in antithrombin. Threonine 85 underlies the opening of the main beta-sheet of the molecule and its replacement, by the polar lysine, in antithrombin Wobble, resulted in a plasma deficiency of antithrombin with an uncharacteristically severe onset of thrombosis at 10 years of age, whereas the replacement of the same residue by a nonpolar methionine, antithrombin Wibble, gave near-normal levels of plasma antithrombin and more typical adult thromboembolic disease. Isolated antithrombin Wibble had a decreased thermal stability (Tm 56.2, normal 57.6 degreesC) but was fully stabilized by the heparin pentasaccharide (Tm 71.8, normal 71.0 degreesC), indicating that the prime abnormality is a laxity in the transition of the main sheet of the molecule from the 5- to 6-stranded form, as was confirmed by the ready conversion of antithrombin Wibble to the 6-stranded latent form on incubation. That this transition can occur in vivo was shown by the finding of nearly 10% of the proband's plasma antithrombin in the latent form and also, surprisingly, of small but definitive amounts of latent antithrombin in normal plasma. The latent transition will be predictably accelerated not only by gross mutations, as with antithrombin Wobble, to give severe episodic thrombosis, but also by milder mutations, as with antithrombin Wibble, to trigger thrombosis in the presence of other predisposing factors, including the conformational stress imposed by the raised body temperatures of fevers. Both antithrombin variants had an exceptional (25-fold) increase in heparin affinity and this, together with an increased inhibitory activity against factor Xa, provides evidence of the direct linkage of A-sheet opening to the conformational basis of heparin binding and activation.     

Q-band (26?40 GHz) GaAs FET single-stage amplifier

The high-frequency S-parameters of a 0.3 ?m-gate-length GaAs FET have been measured and compared with the device equivalent circuit model. From the data a Q-band single-stage low noise (3.1 dB) amplifier was designed.     

Clonal stability in late-relapsing childhood lymphoblastic leukaemia

We report stability of a clonal immunoglobulin heavy chain (IgH) gene rearrangement in a case of childhood acute lymphoblastic leukaemia (ALL) relapsing 17 years after completion of first-line therapy. Clonal stability was shown by polymerase chain reaction amplification of the hypervariable CDRIII region of IgH gene. Identically sized products from the original diagnostic and the second presentation samples were obtained and direct sequencing confirmed complete sequence homology. Absence of clonal evolution together with recent reports of persistent minimal residual disease in patients in long-term complete remission, suggests that 'cure' of childhood ALL may be critically dependent on effective immune surveillance to keep such disease below clinically significant levels.     

Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of diabetic nephropathy

Squamous odontogenic tumour is a benign odontogenic tumour composed of a well-differentiated squamous epithelium immersed in a fibrous connective tissue stroma. It is a rare tumour and a recent literature review yielded only 36 cases. Two cases of squamous odontogenic tumour are presented, 1 located in the maxilla and the other in the mandible: 1 of these cases showed a periodontal involvement. The radiographic picture was fairly characteristic in 1 case, with a radiolucent lesion between the roots of the second mandibular premolar and the first molar, while, in the other case, it was possible to observe the presence of a lesion located at the apex of a molar. The tumours were enucleated, and no recurrences were observed after 5 years.     

Distribution of trace metals in a ling (Genypterus blacodes) fish fillet

The distribution of trace metals in a ling (Genypterus blacodes) fish fillet was determined from ICP-MS measurements of digests prepared using nitric acid and hydrogen peroxide, followed by microwave digestion. Most trace elements were inhomogeneously distributed in the muscle tissue of the ling with a non-linear increase in concentration towards the tail end of the fillet. This distribution pattern may be connected to the size variation of the individual muscle cells or the change in the ratio of connective tissue to muscle tissue, suggesting that the observed inhomogeneity of muscle elemental distribution may be inherent to all fish species. The concentration of an element in a sample of fish muscle tissue thus depends on the physical location within the fish from which the sample was dissected. Significant differences in trace element concentrations were also detected between the red and white muscle fibres of ling, as well as between the belly flap and the rest of the musculature.     

GaAs microlens arrays grown by shadow masked MOVPE

This paper describes the fabrication of high quality GaAs microlenses and microlens arrays using shadow masked metalorganic vapor phase epitaxial (MOVPE) growth (SMMG). Microlenses with apertures as small as 30 μm were fabricated and focal lengths down to 40 μm were measured. The smaller lenses closely fit the theoretical behavior of ideal spherical lenses while larger lenses (focal length >80 μm) showed a more complex physical shape and could not be modeled as spherical. This deviation from a spherical shape is expected from simulation of SMMG. The full width at half maximum of the beam waist was <2 μm for all sizes of microlens indicating that these lenses are compatible with coupling to single mode fibers.