Chronic mucocutaneous candidiasis and primary hypothyroidism in two families

We describe the clinical and immunological features of two families with chronic mucocutaneous candidiasis (CMC) and primary hypothyroidism. Family A includes three siblings with both candidiasis and hypothyroidism and four individuals with hypothyroidism only. Family B includes four members with candidiasis, of whom one (a male child) also had hypothyroidism. All individuals affected with CMC had suffered from oral candidiasis and onychomycosis since infancy. Facial seborrhoic dermatitis, general folliculitis and scaling blepharitis were main manifestations. Hypothyroidism became evident during childhood. No thyroid antibodies were present in the affected siblings in family A, while the male in family B with hypothyroidism had antibodies against thyroid peroxidase at diagnosis. Immunological evaluation revealed intra-individual variations in serum immunoglobulin levels, lymphocyte subsets and proliferative responses, but there were no consistent abnormalities. Vaccine responses were normal. AIRE gene region microsatellite markers did not segregate with disease nor were autoantibodies typical for autoimmune polyendocrine syndrome type 1 detected in the families. Conclusion: the link between hypothyroidism and chronic mucocutaneous candidiasis remains to be identified.Abbreviations AADC aromatic l -amino acid decarboxylase - APS 1 autoimmune polyendocrine syndrome type 1 - CMC chronic mucocutaneous candidiasis - GAD glutamic acid decarboxylase - MBL mannose-binding lectin - 17OH 17-hydroxylase - 21OH 21-hydroxylase - SCC side-chain cleaving enzyme - TG-Ab anti-thyroglobulin antibodies - TPO-Ab anti-thyroperoxidase antibodies     

Validation of a simplified netilmicin dosage regimen in infants

The aim of this study was to validate a simplified high-dosage, extended-interval netilmicin dosage regimen for infants. A total of 129 infants receiving 163 treatment courses of netilmicin (6 mg kg every 24 or 36 h depending on gestational age (GA), postnatal age and postmenstrual age) was analysed. Serum netilmicin concentrations were monitored before (Cmin), 30 min (C0.5h) after and 7.5 h (C7.5h) after the third dose. In 110 patients during first week of life mean C0.5h was 10.5 mg/l. Mean C0.5h was significantly lower (9.0 mg/l) in 38 infants older than 1 week of age. 14 of 15 patients with Cmin levels > or = 2 mg/l receiving netilmicin every 36 h were < 28 weeks of gestation. In the first week of life significant correlations between GA and elimination half-life (p < 0.001) and between plasma creatinine and elevated Cmin (p < 0.002) were found, but no correlation between C0.5h and GA. In this high-dosage regimen a dosing interval of 48 h for GA < 29 weeks, 36 h for GA 29-36 weeks and 24 h for full term babies seems appropriate, during first week of life, to avoid the majority of elevated trough levels and still obtain maximal therapeutic efficacy.     

Immediate and delayed incorporations of events into dreams: further replication and implications for dream function

The incorporation of memories into dreams is characterized by two types of temporal effects: the day-residue effect, involving immediate incorporations of events from the preceding day, and the dream-lag effect, involving incorporations delayed by about a week. This study was designed to replicate these two effects while controlling several prior methodological problems and to provide preliminary information about potential functions of delayed event incorporations. Introductory Psychology students were asked to recall dreams at home for 1 week. Subsequently, they were instructed to select a single dream and to retrieve past events related to it that arose from one of seven randomly determined days prior to the dream (days 1-7). They then rated both their confidence in recall of events and the extent of correspondence between events and dreams. Judges evaluated qualities of the reported events using scales derived from theories about the function of delayed incorporations. Average ratings of correspondences between dreams and events were high for predream days 1 and 2, low for days 3 and 4 and high again for days 5-7, but only for participants who rated their confidence in recall of events as high and only for females. Delayed incorporations were more likely than immediate incorporations to refer to events characterized by interpersonal interactions, spatial locations, resolved problems and positive emotions. The findings are consistent with the possibility that processes with circaseptan (about 7 days) morphology underlie dream incorporation and that these processes subserve the functions of socio-emotional adaptation and memory consolidation.     

Phe-Gly dipeptidomimetics designed for the di-/tripeptide transporters PEPT1 and PEPT2: synthesis and biological investigations

A series of five Phe-Gly dipeptidomimetics containing different amide bond replacements have been synthesized in a facile way from the readily available unsaturated ketoester 1, and their affinities for the di-/tripeptide transporters hPEPT1 (Caco-2 cells) and rPEPT2 (SKPT cells) were tested. The compounds contained the amide bond isosteres ketomethylene (2a), (R)- and (S)-hydroxyethylidene (3a and 4a), and (R)- and (S)-hydroxyethylene (5a and 6a) to provide information on the conformational and stereochemical requirements for hPEPT1 and rPEPT2 affinity. The affinity studies showed that for rPEPT2 there is no significant difference in affinity between the ketomethylene isostere 2a and the natural substrate Phe-Gly (K(i) values of 18.8 and 14.6 microM, respectively). Also the affinities for hPEPT1 are in the same range (K(i) values of 0.40 and 0.20 mM, respectively). This corroborates earlier findings that the amide bond as such is not essential for binding to PEPTX, but the results also reveal possible differences in the binding of ketomethylene isosteres to hPEPT1 and rPEPT2. The trans-hydroxyethylidene and hydroxyethylene isosteres proved to be poor substrates for PEPTX. These results provide new information about the importance of flexibility and of the stereochemistry at the C(4)-position for this class of compounds. Furthermore, the intracellular uptake of 2a-4a in Caco-2 cells was investigated, showing a 3-fold reduction of the uptake of 2a in the presence of the competetive inhibitor Gly-Pro, indicating contribution from an active transport component. No active uptake of 3a and 4a was observed. Transepithelial transport studies also indicated active transport of 2a across Caco-2 monolayers.     

Modified protocols for surfactant therapy in experimental meconium aspiration syndrome

In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50-75 mg kg(-1)) through the airways. When the PaO(2) had decreased to <20 kPa (mean +/- SD 12 +/- 3.9 kPa), the rats were randomly allocated to ten groups (G). G 6-10 underwent lung lavage with diluted Curosurf (5 mg ml(-1), 20 ml kg(-1)), whereas G 1-5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg(-1)), and G 3 and 8 received Curosurf (100 mg kg(-1)) plus dextran (75 mg kg(-1)); G 4 and 9 received Curosurf (200 mg kg(-1)), and G 5 and G 10 received Curosurf (200 mg kg(-1)) plus dextran (75 mg kg(-1)). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO(2) transiently increased to 30-40 kPa. In G 4, 5, 9, and 10, the PaO(2) remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg(-1)) was nevertheless required to optimize gas exchange.     

The effect of two configuration factors,time, and thermal cycling on resin to dentin bond strengths

Most in vitro testing of bonding systems is performed using specimens made in a mold with a low configuration (C) factor (ratio of bonded/unbonded surfaces) whereas clinically the C-factor is usually much greater. This study compared the effect of thermal cycling on the measured shear bond strength of 3M Single Bond dental adhesive bonded to dentin using molds with two different C-factors. The hypothesis was that neither C-factor nor thermal cycling would affect measured bond strengths. Resin composite was bonded to human dentin in cylindrical molds with an internal diameter of 3.2mm and either 1mm or 2.5mm deep. The 1mm deep molds had a C-factor of 2.2 and the 2.5mm deep molds had a C-factor of 4.1. Specimens were debonded either 10min after they had been bonded to dentin, or after they had been stored for 7 days in water at 37+/-1 degrees C, or after thermal cycling 5000 times for 7 days. Two-way ANOVA showed that overall both the C-factor and the storage condition had a significant effect on bond strength (p<0.001). There was a significant interaction (p<0.001) between the C-factor and how the specimens had been stored. The GLM/LSMEANS procedure with Sidak's adjustment for multiple comparisons showed that overall the specimens made in the mold with a high C-factor (4.1) had a lower bond strength than those that had been made in the mold with a lower (2.2) C-factor (p<0.001). Thermal cycling had a negative effect on the bond strength only for specimens made in molds with a C-factor of 4.1 (p<0.001).