The poor prognosis of intubated COPD patients with IPA, in spite of antifungal treatment suggests that further studies are required to define the limits and indications for ICU management of these patients.

1 The vasodilator and antihypertensive properties of pinacidil, cromakalim (BRL 34915), nicorandil and minoxidil sulphate may be due, at least in part, to their ability to open K+ channels in vascular smooth muscles. In this study, mouse pancreatic islets were used to determine whether these drugs affect insulin release by acting on K + channels of fl-cells. Their effects were compared to those of diazoxide. 2 Diazoxide caused a dose-dependent inhibition of insulin release by islets incubated with 15mM glucose (93% at 1OOM). Pinacidil inhibited release by 36 and 72% at 100 and 500 M, respectively.Cromakalim and nicorandil were less effective (35 and 25% inhibition at 50OpM). Minoxidil sulphate increased insulin release at 500 pM. 3 In the presence of 7mm glucose and in the absence of Ca2+ (to avoid activation of Ca2+-dependent K+ channels), 86Rb efflux from islet cells was increased by 100-50OM pinacidil and 5OM nicorandil, which were, however, less potent than diazoxide. Cromakalim was ineffective, whereas 5OM minoxidil sulphate decreased the efflux rate. In the absence of glucose and presence of Ca2", 500 JIM cromakalim and minoxidil sulphate inhibited 86Rb efflux. 5 ATP-sensitive K+ currents were studied in single fl-cells by the whole cell patch-clamp technique. Pinacidil increased the current less than did diazoxide. In contrast, cromakalim and minoxidil sulphate decreased K+-currents whilst nicorandil was without effect. 6 It is concluded that pinacidil, like diazoxide, inhibits insulin release from fl-cells by opening ATP-sensitive K+ channels, whereas the smaller inhibitory effects of cromakalim and nicorandil may involve actions other than on K+ channels in these cells. Minoxidil sulphate potentiates glucose-induced insulin release, probably by inhibiting ATP-sensitive K+ channels. However, all these effects of the vasodilators are only seen at high concentrations and are thus unlikely to occur in vivo.

HB 699 is a benzoic acid derivative similar to the non-sulphonylurea moiety of glibenclamide. The mechanisms whereby it affects B-cell function have been studied in vitro with mouse islets. In the presence of 3 mmol/l glucose, HB 699 decreased 86Rb+ efflux and accelerated 45Ca2+ efflux from islet cells, depolarized the B-cell membrane and induced an electrical activity similar to that triggered by stimulatory concentrations of glucose, and increased insulin release. The changes in 45Ca2+ efflux and insulin release, but not the inhibition of 86Rb+ efflux, were abolished in the absence of Ca2+. In the presence of 10 mmol/l glucose, HB 699 increased 86Rb+ and 45Ca2+ efflux from the islets, caused a persistent depolarization of the B-cell membrane with continuous electrical activity and markedly potentiated insulin release. All these changes were suppressed by omission of extracellular Ca2+. In the presence of 15 mmol/l glucose, diazoxide increased 86Rb+ efflux, hyperpolarized the B-cell membrane, suppressed electrical activity and inhibited insulin release. HB 699 reversed these effects of diazoxide. It is suggested that HB 699 decreases K+ permeability of the B-cell membrane, thereby causing a depolarization which leads to activation of voltage-dependent Ca channels and Ca2+ influx, and eventually increases insulin release. A sulphonylurea group is thus not a prerequisite to trigger the sequence of events that is also thought to underlie the releasing effects of tolbutamide and glibenclamide.

The purpose of this study was to characterise Lyme meningitis (LM) in a Belgian paediatric population and to suggest findings that could allow early distinction from aseptic meningitis (AM). The medical records of patients hospitalised between 1993 and 2000 and with a discharge diagnosis of LM (n=14) or AM (n=16) were retrospectively reviewed. The Kruskal-Wallis test was used to compare data. Of the patients, 16 were identified with AM and 14 with LM, amongst which 7 presented with isolated LM and 7 with associated peripheral facial palsy (PFP). Patients with AM, when compared with LM, complained of more pronounced signs and symptoms of meningitis (fever, headaches, and neck stiffness); they statistically displayed a shorter period of symptoms before admission (1.6 vs 15 days), higher neutrophilic component (mean 56% vs 2.4%), and lower protein levels (mean 0.39 vs 1.12 g/l) on cerebrospinal fluid analysis. In the neuroborreliosis group, the duration of symptoms was shorter and the cerebrospinal protein level was lower in cases of LM associated with PFP compared to isolated LM (mean 1.3 vs 15 days; mean 0.55 g/l vs 1.12 g/l). Conclusions. Our results suggest that some clinical data and laboratory findings may help the physician to diagnose aseptic or Lyme meningitis before completion of serologic testing. LM should be suspected in cases of meningitis with very low CSF neutrophilic counts and high protein levels associated with prolonged duration of symptoms, low grade fever, and absence of pronounced signs of meningitis.

1 Mouse islets were used to define the characteristics and study the mechanisms of the stimulation of insulin release by compound 2 At a non-stimulatory concentration of glucose (3 mM), (-)-AZ-DF 265 reversibly inhibited 'Rb efflux from islet cells, depolarized the P-cell membrane, induced electrical activity, stimulated 45Ca efflux, and triggered insulin release. Maximum inhibition of 'Rb efflux occurred at 0.03 tiM (-)-AZ-DF 265, whereas the threshold concentration for stimulation of release was 0.1 M. Omission of extracellular Ca2" abolished all effects of the drug but the inhibition of 86Rb efflux. 3 At a stimulatory concentration of glucose (10mM), (-)-AZ-DF265 reversibly increased 86Rb efflux, potentiated electrical activity, augmented 45Ca efflux, and increased insulin release. Maximum stimulation of 'Rb efflux and insulin release was obtained with 0.03 pM (-)-AZ-DF 265. Omission of extracellular Ca2" abolished all effects of the drug. 4 The potency of (-)-AZ-DF 265 was similar to that of glibenclamide, whereas the (+ )-enantiomer was about 10 times less potent on 86Rb efflux and insulin release. 5 It is concluded that, like sulphonylureas, compound AZ-DF 265 decreases K+ permeability of the P-cell membrane and thereby causes depolarization. This activates voltage-dependent Ca channels, permits Ca2" influx and eventually stimulates insulin release. Its stereoselectivity may help to elucidate the mechanisms of K channel blockade and, hence, lead to the design of more potent and specific insulinotropic drugs.

From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (107, 105 and 103 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions.

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1 Adamantane derivatives were found to increase insulin release in vitro. Mouse islets were used to study the mechanisms and molecular requirements of that hitherto unrecognised property.2 At a non-stimulatory concentration of glucose (3mM), 1-adamantanamine (1 mM) reversibly inhibited`6Rb efflux from islet cells, depolarized the P-cell membrane, induced electrical activity, stimulated 45Ca uptake and efflux, and triggered insulin release. Omission of extracellular Ca2" abolished the secretory response but only partially inhibited the acceleration of 45Ca efflux.3 At a stimulatory concentration of glucose (10 mM), 1-adamantanamine reversibly increased '8Rb efflux, potentiated electrical activity (lengthening of the slow waves with spikes), augmented 45Ca uptake and efflux, and increased insulin release. The effects of adamantanamine were dose-dependent, with a threshold concentration of 1O iM for stimulation of release. 4 2-Adamantanamine was as potent as l-adamantanamine. In contrast, substitution of the amino group by a carboxyl group (l-adamantanecarboxylic acid) decreased the effectiveness by about 65%, and substitution by a hydroxyl group (1-adamantanol) suppressed it.