Joule spectroscopy of hybrid superconductor-semiconductor nanodevices.

Hybrid superconductor-semiconductor devices offer highly tunable platforms, potentially suitable for quantum technology applications, that have been intensively studied in the past decade. Here we establish that measurements of the superconductor-to-normal transition originating from Joule heating provide a powerful spectroscopical tool to characterize such hybrid devices. Concretely, we apply this technique to junctions in full-shell Al-InAs nanowires in the Little-Parks regime and obtain detailed information of each lead independently and in a single measurement, including differences in the superconducting coherence lengths of the leads, inhomogeneous covering of the epitaxial shell, and the inverse superconducting proximity effect; all-in-all constituting a unique fingerprint of each device with applications in the interpretation of low-bias data, the optimization of device geometries, and the uncovering of disorder in these systems. Besides the practical uses, our work also underscores the importance of heating in hybrid devices, an effect that is often overlooked.

Yu-Shiba-Rusinov screening of spins in double quantum dots.

A magnetic impurity coupled to a superconductor gives rise to a Yu-Shiba-Rusinov (YSR) state inside the superconducting energy gap. With increasing exchange coupling the excitation energy of this state eventually crosses zero and the system switches to a YSR ground state with bound quasiparticles screening the impurity spin by h/2. Here we explore indium arsenide (InAs) nanowire double quantum dots tunnel coupled to a superconductor and demonstrate YSR screening of spin-1/2 and spin-1 states. Gating the double dot through nine different charge states, we show that the honeycomb pattern of zero-bias conductance peaks, archetypal of double dots coupled to normal leads, is replaced by lines of zero-energy YSR states. These enclose regions of YSR-screened dot spins displaying distinctive spectral features, and their characteristic shape and topology change markedly with tunnel coupling strengths. We find excellent agreement with a simple zero-bandwidth approximation, and with numerical renormalization group calculations for the two-orbital Anderson model.

Supercurrent in a Double Quantum Dot.

We demonstrate the Josephson effect in a serial double quantum dot defined in a nanowire with epitaxial superconducting leads. The supercurrent stability diagram adopts a honeycomb pattern. We observe sharp discontinuities in the magnitude of the critical current, I_{c}, as a function of dot occupation, related to doublet to singlet ground state transitions. Detuning of the energy levels offers a tuning knob for I_{c}, which attains a maximum at zero detuning. The consistency between experiment and theory indicates that our device is a faithful realization of the two-impurity Anderson model.

[Peroral drug administration to children--are there any problems?]. / Peroral medicinsk behandling af børn--er der problemer?

Children's compliance with orally administered medicine is described. Five hundred questionnaires were given to the parents of children at their first visit at the out-patient clinic with a response from 484. Three hundred and ninety-seven children had been treated with oral medication in the form of liquid formulation or tablets, 257 within the previous year. Of these, 43.2% reported difficulties in taking the medication. Only 8.5% of the treatments had been interrupted. The main cause of the problems were the medications' taste and difficulties with swallowing tablets. The problems were more pronounced among the younger children. The administration of tablets was more difficult than the administration of liquids. There was no relationship between the problems and frequency of dosing, duration of treatment, severity of illness, social status of the parents, or the parents' age. In conclusion, prescription of better tasting mixtures and chewable tablets may reduce the problems associated with administering oral medication to children.

Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly.

OBJECTIVE: The purpose of the present study was to compare the dosage requirements of recombinant human erythropoletin (rHuEPO) administered subcutaneously (SC) either one or three times weekly. DESIGN: A randomized, prospective study. SETTING: The patients were recruited from two university hospitals and five county hospitals. PATIENTS: Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal failure completed the study. INTERVENTIONS: Initially, all were treated with rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B). MAIN OUTCOME MEASURES: The Hb levels and rHuEPO doses at the start and at the end of the three-month study period. RESULTS: In group A the median Hb at randomization was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and 114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95) U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to 77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks. CONCLUSIONS: Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen.

Evidence that treatment of ESRD patients with recombinant human erythropoietin induces immunosuppression without affecting the distribution of peripheral blood mononuclear cell subpopulations.

Fifteen patients with end-stage renal disease (ESRD) were blood sampled before and 1-, 2-, 3-, and 6 months after institution of recombinant human erythropoietin (r-HuEPO) therapy. Subpopulations of immunocompetent peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry using monoclonal antibodies against various T-lymphocyte antigens, B-lymphocytes, natural killer (NK)-cells, monocytes, and macrophages, and finally bone marrow progenitor cells. Functional properties of peripheral T-lymphocytes were analyzed by proliferation assays with mitogens, alloantigens and microbiological antigens. All patients but 3 responded with sufficient correction of the anaemia. The absolute number of leucocytes and lymphocytes remained unchanged during the study. Likewise, a remarkable intraindividual months to month constancy in the relative distribution of all PBMC subsets analyzed was recorded during the observation period, although some interindividual variability was observed. In contrast, the T-lymphocyte responsiveness decreased significantly except for 2 out of 11. We conclude, that treatment of renal anemia with r-HuEPO seems to induce immunosuppression in ESRD patients without affecting the distribution of various PBMC subsets.

The influence of orally deposited budesonide on the systemic availability of budesonide after inhalation from a Turbuhaler.

1. The aim of this pharmacokinetic study was to evaluate to what extent oropharyngeal deposition of drug contributes to the systemic availability of budesonide inhaled from a dry powder inhaler (Turbuhaler). 2. The design was a randomized cross-over study in eight children aged 7-13 years. The plasma concentrations of the two epimers of budesonide (22R and 22S) after inhalation of 1 mg budesonide from a Turbuhaler were compared with the plasma concentrations obtained when the absorption of the drug deposited in the oropharynx was blocked by drinking and rinsing the mouth with charcoal before and after the inhalation. 3. The plasma concentrations of budesonide were significantly reduced by the charcoal treatment (P < 0.01) and the area under the time vs plasma concentration curve 0-4 h was significantly reduced from 9.5 to 8.0 mmol l-1 h for 22S (P < 0.01) and from 7.6 to 5.7 mmol l-1 h for 22R (P < 0.01). 4. The plasma concentrations and the AUCs after both Turbuhaler administrations were markedly higher than those obtained in earlier studies using other inhalers suggesting a higher intrapulmonary deposition of drug after Turbuhaler treatment. 5. It is concluded that oropharyngeal deposition of drug accounts for about 20% of the total systemic availability of budesonide inhaled from Turbuhaler. Thus, the main contribution to the system comes from budesonide absorbed in the airways.

Does erythropoietin cause hormonal changes in haemodialysis patients?

In 10 female and 10 male haemodialysis patients plasma FSH, LH, testosterone, prolactin, and somatotropin (STH) were estimated during erythropoietin (rHuEpo) treatment for 6 months. All but one patient responded with an increase in haemoglobin. The patients experienced improved sexual function according to the answers given in a self-administered questionnaire. Of the 90% who answered before the study 22% could not perform sexual activities whether they wanted to or not. During and at the end of the study 80 and 60% respectively answered, and none had these problems. In contrast, serum values of the sexual hormones (FSH, LH, testosterone and prolactin) were not significantly changed during rHuEpo therapy, and neither was the basal plasma STH.

Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin.

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.

Congenital nephrotic syndrome associated with Lowe's syndrome.

Two cases of the oculo-cerebro-renal syndrome of Lowe are reported, in which the course of the disease was very fast and unusual. Within the first hours after birth the patients developed nephrotic syndrome and died at the age of 45 and 4 days, respectively. Renal tissue obtained by biopsy and at autopsy disclosed pronounced glomerular changes.

Nephrotic syndrome in the first three months of life.

When the nephrotic syndrome develops within the first 3 months of life it is considered as congenital. In a review, different types of renal diseases are found behind the syndrome in early infancy. A classification of these is proposed, based on clinicopathology. Five classes with subgroups are described, and the necessity of recognizing these for prognosis, therapy and genetic counselling is emphasized.

Renal medullary cystic disease. Findings at urography and ultrasonography.

Medullary cystic disease (MCD) is an uncommon renal disease with adult onset and autosomal inheritance, eventually progressing to terminal renal failure. It may be difficult to identify because of insufficient diagnostic tools. At urography, the same ring-shaped accumulation of contrast medium at the corticomedullary junction was observed in two patients (mother and son) suffering from MCD. To our knowledge this observation has not been reported before.

Simplified immunoglobulin treatment of idiopathic thrombocytopenic purpura.

The recommended dose of intravenous IgG for idiopathic thrombocytopenic purpura has been 0.4 g/kg on 5 consecutive days. A simplified approach, giving a single infusion of 0.8-1.0 g/kg over 8 hours, has been tried in a series of 11 children with newly diagnosed disease. In 8 cases the infusion produced a prompt platelet response culminating at 128-502 X 10(9)/l after 3-13 days, and 4 of these cases required no further treatment while 2 needed a booster infusion due to an early relapse and 2 followed a chronic course. In 3 cases platelet responses were poor in spite of supplementary doses to a total of 1.4-2.0 g/kg: 2 infants failed to achieve normal platelet counts and 1 case with fulminant bleeding manifestations proved completely resistant. Significant side effects were not observed. These results indicate that IgG-therapy practically may be initiated with a single infusion, the resulting platelet response indicating the need for further infusions.

Absorption characteristics of once-a-day slow-release theophylline preparation in children with asthma.

The single- and multiple-dose absorption characteristics of a new sustained-release theophylline preparation, which has been formulated for once per day dosing in adults, were investigated in children aged 8 to 14 years. Four single doses were studied, each dose separated by 1 week. During steady state the preparation was given once daily in the morning for 1 week, and serum theophylline concentration was determined through two dosing intervals (48 hours). The product showed excellent sustained-release characteristics and consistent absorption profiles, which were not affected to any clinically important extent by the intake of various meals. After single doses, only 77% to 91% of the product was absorbed during the first 28 hours after dosing. However, bioavailability was complete both after single doses and during steady state. Eight of 14 children had steady-state fluctuations in serum theophylline levels of less than 90% when given doses once daily. Steady-state day-to-day variations in serum theophylline profiles were small in all patients except one, in whom differences up to 33 mumol/L (6 micrograms/mL) were seen (8 hours after dosing). We conclude that this formulation is completely absorbed at a sufficiently slow and consistent rate to permit acceptable fluctuations in absorption with once daily dosing for many, but not all, patients. However, it should not be used in very young children until bioavailability has been studied in this age group.

Pharmacokinetics of budesonide in children with asthma.

The pharmacokinetics of the glucocorticoid budesonide was studied in 6 children with asthma after i.v. injection of 0.5 mg and oral inhalation of 1 mg as an aerosol. Budesonide is a 1:1 mixture of the epimers 22 S and 22 R, which were assayed separately by HPLC combined with RIA. All pharmacokinetic parameters of the epimers differed except the half-life of about 1.5 h. It was significantly shorter than that reported in adults. Plasma clearance averaged 103 l X h-1 for epimer 22 R and 74 l X h-1 for epimer 22 S; calculated per kg body weight these values were about 50% higher than in adults. The difference was about 40% when calculated per m2 of body surface area. Since budesonide is a high-clearance drug, the data indicate higher liver blood flow X kg-1 body weight and m2 of body surface area in children. The systemic availability of the aerosol was approximately 30% of nominal dose, i.e. the same as in adults. The high clearance and short half-life of budesonide in children are advantageous in reducing the risk of possible systemic side-effects of prophylactic treatment of asthma in childhood.