Orlistat: in the prevention and treatment of type 2 diabetes mellitus.

Orlistat is a nonsystemically acting gastric and pancreatic lipase inhibitor that limits the absorption of dietary fat. A retrospective pooled analysis of three 2-year, double-blind, randomised, placebo-controlled trials involving patients with obesity revealed that orlistat recipients were more likely to experience an improvement, and less likely to experience a deterioration, in glucose tolerance status than placebo recipients. In comparison with placebo, orlistat recipients had significantly greater reductions in glycosylated haemoglobin and fasting plasma glucose levels in large, double-blind, randomised, placebo-controlled studies of 24 to 52 weeks' duration involving patients with obesity and type 2 diabetes mellitus. In one such study, the dosage of concomitant sulphonylureas was able to be reduced in more orlistat than placebo recipients (43.2 vs 28.9%), with discontinuation of sulphonylurea therapy achieved in 11.7% of orlistat recipients. The most common adverse effects reported in orlistat recipients with type 2 diabetes mellitus relate to the gastrointestinal system and are similar to those reported in studies involving patients without type 2 diabetes mellitus.

Methylphenidate (OROS formulation).

Methylphenidate is a CNS stimulant that is thought to block the reuptake of dopamine and noradrenaline (norepinephrine) into the presynaptic neuron. A sustained release (OROS formulation of the drug has been developed for use in children with attention deficit/hyperactivity disorder (ADHD). In children aged 6 to 12 years with ADHD, the maximum plasma concentration of OROS methylphenidate 18 to 54 mg was reached after approximately 7 to 8 hours. In adults, the plasma concentration-time profile of OROS methylphenidate differed markedly from that of the sustained release and immediate release (IR) methylphenidate formulations. In a clinical trial involving 282 children with ADHD, once daily OROS methylphenidate 18 to 54 mg was significantly more effective than placebo and demonstrated an effect similar to IR methylphenidate 5 to 15 mg 3 times daily in reducing the symptoms of ADHD. OROS methylphenidate demonstrated sustained efficacy in a 1-year noncomparative study involving children with ADHD. In clinical trials, the OROS formulation of methylphenidate had a tolerability profile similar to that of IR methylphenidate.

Caspofungin.

Caspofungin is the first in a new class of antifungal agents, the glucan synthesis inhibitors, that interfere with fungal cell wall synthesis. Caspofungin exhibited in vitro and in vivo efficacy against a wide range of fungi and yeasts including Aspergillus and Candida species. A complete or partial response to caspofungin therapy was seen in 40.7% of immunocompromised adults with invasive aspergillosis who did not respond to, or did not tolerate, other antifungal agents in a noncomparative multicentre study. Caspofungin was effective in patients with oropharyngeal or oesophageal candidiasis, according to the preliminary results of 2 randomised double-blind trials. Caspofungin was generally well tolerated in a multicentre noncomparative trial involving patients with invasive aspergillosis. One or more drug-related clinical adverse effects were experienced by 13.8% of caspofungin recipients (the most common were fever, nausea, vomiting and complications associated with the vein into which caspofungin was infused). The tolerability of caspofungin appeared to be better than that of amphotericin B and similar to that of fluconazole in double-blind, randomised trials involving patients with mucosal candidiasis.

The structure of the upper atmosphere of mars: In situ accelerometer measurements from mars global surveyor

The Mars Global Surveyor (MGS) z-axis accelerometer has obtained over 200 vertical structures of thermospheric density, temperature, and pressure, ranging from 110 to 170 kilometers, compared to only three previous such vertical structures. In November 1997, a regional dust storm in the Southern Hemisphere triggered an unexpectedly large thermospheric response at mid-northern latitudes, increasing the altitude of thermospheric pressure surfaces there by as much as 8 kilometers and indicating a strong global thermospheric response to a regional dust storm. Throughout the MGS mission, thermospheric density bulges have been detected on opposite sides of the planet near 90 degreesE and 90 degreesW, in the vicinity of maximum terrain heights. This wave 2 pattern may be caused by topographically-forced planetary waves propagating up from the lower atmosphere.

Area variation of avoidable causes of death in Auckland, 1977-85.

An area analysis is presented of deaths in Auckland that were ostensibly avoidable, by appropriate medical intervention and treatment. Mortality data from the National Health Statistics Centre for the period 1977-85 were used in the analysis. The definition of an avoidable death was based on the International Classification of Diseases (ICD) code using established criteria. Eight percent of deaths of people under 65 years of age met the criteria. The basic spatial entity for the analysis is the census area unit and maps of Auckland are presented to show the distribution of avoidable mortality. It is found that there are significant and consistent spatial variations. Three areas with avoidable mortality that is generally higher than elsewhere are apparent: in south Auckland; to the north-west of the central urban sector centered on Grey Lynn; and in the eastern parts of the central sector from Glenn Innes to Onehunga.

Short-term cyclic variations and diurnal variations of the venus upper atmosphere.

Measurements of satellite drag obtained from the orbital decay of the Pioneer Venus orbiter on the nightside of Venus indicate an atomic oxygen atmosphere near 155 kilometers (an order of magnitude less dense than expected) with nighttime inferred exospheric temperatures averaging as low as 110 K. Densities at these altitudes decrease sharply from day to night, contrary to the predicted nighttime oxygen bulge. This decrease may be indicative of an unexpectedly weak transport across the evening terminator or a very strong heat sink at night that is possibly related to vertical eddy heat transport. Large periodic oscillations in density and inferred exospheric temperature are detected with a period of 5 to 6 days. We have subsequently discovered temperature variations of the same period in the stratosphere, which are tentatively interpreted as planetary-scale waves that may propagate upward producing the periodic variations in the thermosphere and exosphere. The peak-to-peak amplitude of the temperature oscillations associated with these waves apparently increases with altitude approximately as follows: 1 K (70 kilometers), 3 K (90 kilometers), 40 K (155 kilometers). Inferred nighttime exospheric temperatures are found to be asymmetric relative to midnight, minimizing on the morning side. The possibility of superrotation of the thermosphere, and exosphere is discussed.

Venus thermosphere and exosphere: first satellite drag measurements of an extraterrestrial atmosphere.

Atmospheric drag measurements obtained from the study of the orbital decay of Pioneer Venus 1 indicate that atomic oxygen predominates in the Venus atmosphere above 160 kilometers. Drag measurements give evidence that conditions characteristic of a planetary thermosphere disappear near sundown, with inferred exospheric temperatures sharply dropping from approximately 300 K to less than 150 K. Observed denisities are generally lower than given by theoretical models.