Search for Lepton Number and Flavor Violation in K

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Variation in rod and cone density from the fovea to the mid-periphery in healthy human retinas using adaptive optics scanning laser ophthalmoscopy.

PurposeTo characterize the rod and cone photoreceptor mosaic at retinal locations spanning the central 60° in vivo using adaptive optics scanning laser ophthalmoscopy (AO-SLO) in healthy human eyes.MethodsAO-SLO images (0.7 × 0.9°) were acquired at 680 nm from 14 locations from 30° nasal retina (NR) to 30° temporal retina (TR) in 5 subjects. Registered averaged images were used to measure rod and cone density and spacing within 60 × 60 µm regions of interest. Voronoi analysis was performed to examine packing geometry at all locations.ResultsAverage peak cone density near the fovea was 164 000±24 000 cones/mm(2) and decreased to 6700±1500 and 5400±700 cones/mm(2) at 30° NR and 30° TR, respectively. Cone-to-cone spacing increased from 2.7±0.2 µm at the fovea to 14.6±1.4 µm at 30° NR and 16.3±0.7 µm at 30° TR. Rod density peaked at 25° NR (124 000±20 000 rods/mm(2)) and 20° TR (120 000±12 000 rods/mm(2)) and decreased at higher eccentricities. Center-to-center rod spacing was lowest nasally at 25° (2.1±0.1 µm). Temporally, rod spacing was lowest at 20° (2.2±0.1 µm) before increasing to 2.3±0.1 µm at 30° TR.ConclusionsBoth rod and cone densities showed good agreement with histology and prior AO-SLO studies. The results demonstrate the ability to image at higher retinal eccentricities than reported previously. This has clinical importance in diseases that initially affect the peripheral retina such as retinitis pigmentosa.

Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of cross-reactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase.

The recent cloning of the thyroid peroxidase (TPO) has shown that it is identical to the thyroid microsomal antigen (TMA), a potent antigen involved in autoimmune thyroid disease (ATD), which shares significant sequence homology with myeloperoxidase. The present study shows that autoantibodies (aAb) to the TMA/TPO antigen cross-react with human leucocyte myeloperoxidase, bovine lactoperoxidase and horseradish peroxidase. Cross-reactivity to myeloperoxidase was only apparent by ELISA using reduced and alkylated antigen preparations or by immunoblotting following denaturation with SDS. Sequential absorption of sera on SDS-denatured thyroid microsomes immobilized on Sepharose-4B followed by absorption on native microsomes removed all aAb specificities to TMA/TPO and the three peroxidase preparations, giving compelling evidence on the genuine cross-reactive nature of these aAbs. Sera from different patients contain different qualitative and quantitative specificities of aAb to the TMA/TPO antigen, confirming the polyclonal nature of this autoimmune response.

Pharmacokinetic study of the interaction between rifampicin and ketoconazole.

This study assessed the potential pharmacokinetic interaction between rifampicin and ketoconazole, two drugs used to treat the increasingly common combination of Mycobacterium tuberculosis and Candida albicans infection in AIDS patients. The peak plasma rifampicin concentrations in six healthy male subjects were not altered when taken in conjunction with ketoconazole. However, the peak plasma ketoconazole levels were significantly diminished when taken in conjunction with rifampicin, compared to when taken alone (P less than 0.015). The mean area under the curve (AUC) for ketoconazole was significantly diminished when taken with oral or intravenous rifampicin (P less than 0.001).

Autoantibodies to the thyroid microsomal/thyroid peroxidase antigen are polyclonal and directed to several distinct antigenic sites.

A detailed examination of the epitopes recognized by autoantibodies (aAbs) to the thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) in patients with thyroid autoimmune disease has been made using a combination of immunochemical and enzymatic techniques. Our results demonstrate the the autoimmune response to thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) is multifocal and far more heterogeneous than hitherto recognized. By immunoblotting with aAbs, antigenic determinants on the TMA/TPO have been recognized that are either susceptible to polypeptide denaturation and/or sensitive to the effects of reducing agents. Furthermore, these aAbs can inhibit, to varying degrees, the enzymatic activity of solubilized preparations of TPO in microsomes, as ascertained by peroxidation of guaiacol and iodide. A large proportion of the autoimmune response is directed to the guaiacol peroxidation site. The data support the view that the autoimmune reactivity to the TMA/TPO is a specific polyclonal response with a minimum of six distinct, independent determinants that are recognized by aAbs.

Anticoagulation control with warfarin by junior hospital doctors.

Anticoagulation control in hospital inpatients was monitored in a prospective study. Only 47% of the blood results were within the therapeutic range which is presently recommended.

Systemic absorption of inhaled epinephrine.

To determine the systemic absorption of epinephrine when it is given by inhalation, six normal volunteers were given 15 puffs, followed by 30 puffs, of epinephrine from a pressurized aerosol (160 micrograms epinephrine/puff). The peak mean (+/- SE) plasma epinephrine levels were 1.50 (+/- 0.61) and 4.22 (+/- 1.93) nmol/L 1 minute after each dose, respectively. The effect on physiologic finger tremor correlated with the plasma epinephrine level and returned to baseline 20 minutes after taking the higher dose. There was a small fall in mean plasma potassium levels of 0.45 mmol/L and a small rise in plasma glucose levels of 0.81 mmol/L. On a separate occasion an injection of 0.3 ml of 1/1000 (300 micrograms) epinephrine was given subcutaneously to the same individuals. This caused a peak plasma epinephrine level of 2.43 (+/- 0.47) nmol/L at 10 minutes, and this was still raised at 2.05 (+/- 0.41) nmol/L after 40 minutes. The maximum fall in the mean plasma potassium level was 0.43 mmol/L after the injection.

Urgent coronary artery bypass surgery in the presence of Dressler's syndrome.

The clinical features of Dressler's syndrome which developed in a patient following a third myocardial infarction responded to a short course of prednisolone. However, angina at rest precipitated urgent coronary artery bypass surgery and pericardectomy.

Late presentation of ventricular septal defect following myocardial infarction: the role of non-invasive methods.

A 64-year-old man presented with biventricular failure 5 months after an acute antero-apical myocardial infarction. On auscultation of the praecordium a loud pansystolic murmur was heard. The use of non-invasive studies in diagnosing post-myocardial infarction ventricular septal defect is discussed.

Pulmonary Mycobacterium tuberculosis in acquired immune deficiency syndrome.

A case of pulmonary infection with Mycobacterium tuberculosis in a patient with the acquired immune deficiency syndrome (AIDS) was studied. Diagnosis of AIDS was confirmed by the finding of pulmonary M tuberculosis with oral and oesophageal candidiasis accompanied by characteristic immunological changes with evidence of infection with human T cell lymphotropic virus III. Treatment of this patient was complicated by an unusual drug interaction between rifampicin and ketoconazole, leading to subtherapeutic serum concentrations and poor clinical response to treatment. Intravenous treatment was more effective than oral treatment. This drug interaction should be studied in greater detail as ketoconazole and rifampicin may be used together to treat patients with candidiasis and infection with M tuberculosis.