ACHN-490 is an aminoglycoside with activity against multidrug-resistant pathogens, including those resistant to currently used aminoglycosides. Two randomized, double-blind, placebo-controlled clinical studies investigated the pharmacokinetics (PK), safety, and tolerability of ACHN-490 injection in healthy subjects. Study 1 used a parallel-group design with escalating single (SD) and multiple doses (MD). Study 2 explored a longer duration of the highest dose tolerated in the first study. Subjects were randomly assigned to receive either ACHN-490 injection or a placebo administered by a 10-min intravenous infusion. Study 1 enrolled 39 subjects (30 active and 9 placebo) and consisted of a single dose of 1 mg/kg body weight followed by ascending SD and MD cohorts of 4, 7, 11, and 15 mg/kg for 10, 10, 5, and 3 days, respectively. Study 2 enrolled 8 subjects

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The authors compared the effect of several doses an oral corticosteroid on symptom profile and severity in ragweed hay fever. Thirty-one patients were randomized to receive 0, 6, 12, or 24 mg methylprednisolone (Medrol Tablets [MP], Upjohn, Kalamazoo, MI). A baseline week in which no treatment was given preceded the treatment comparison. At the end of this week, symptom diaries showed that most of the subjects were experiencing moderate or severe symptoms. The corticoid produced dose-related reduction in all symptoms. The difference between placebo and 24 mg MP was significant for all the symptoms monitored, except itching, which benefited marginally. With 6 mg MP, congestion, drainage, and eye symptoms showed significant drug-placebo differences but itching, running/blowing, and sneezing did not. Not all rhinitis symptoms responded equally to corticoid treatment. Those that responded least could reflect histamine effect, which was not effectively suppressed by low-dose, short-term corticoid treatment.

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 pg) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a signifcant (P < 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 jug histamine followed by 10 gtg desmopressin; normal saline followed by 10 ,g desmopressin; 20 Mg histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103±24 vs. 4±17%, mean±SEM, P < 0.02), initial urine osmolality (520±123 vs. 333±75 mosM, P < 0.03), urine electrolyte (potassium, 45±11 vs. 28±7 meq/liter, sodium, 68±21 vs. 36±8 meq/liter, P < 0.03) and creatinine concentrations (95±23 vs. 60±13 mg/dl, P < 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.

Abstract. As part of a long-term effort to both improve access to information on climate change and freshwater resources, and to understand the state of the science, we compiled an electronic bibliography of scientific literature in that area. We analyzed the distribution of information on climatic impacts on freshwater resources, with an emphasis on differences between developed and developing regions as well as differences in the types and focus of research carried out among regions. There has been more research overall in developed countries than in the developing world. Proportionally more of the available research on natural and human systems pertains to developed regions, while most of the analysis done in developing countries is limited to higher-level climatology and hydrology. We argue that scientific information and understanding are important elements of the ability to adapt to potential climatic changes. The distribution of the scientific literature in our database suggests that the types of science most directly relevant to adaptive capacity are skewed towards developed countries, which may exacerbate existing disparities in adaptive capacity, and ultimately worsen the consequences of climatic impacts in developing countries.