Intraoral chilling versus oral sumatriptan for acute migraine.

Migraine pathophysiology is associated with a dural inflammation. Recent evidence suggests that the primary inflammation occurs in a maxillary nerve segment, accessible intraorally. Local tenderness, related to symptom laterality, has been palpated consistently in asymptomatic migraine patients, and significant migraine relief has been obtained from chilling confined to this area. Thirty-five symptomatic episodic migraine patients were enrolled in this study, comparing 40 minutes of bilateral intraoral chilling, 50 mg of oral sumatriptan, and 40 minutes of sham (tongue) chilling. Hollow metal tubes chilled by circulating ice water were held in the maxillary molar periapical areas by the patient. Pain and nausea were recorded at baseline and 1, 2, 4, and 24 hours after start of treatment, using a numeric symptom-relief scale. Significant mean headache relief was obtained by maxillary chilling and sumatriptan at all four time intervals, with poor relief obtained by placebo. Maxillary chilling was more effective than sumatriptan at all four time intervals. Significant nausea relief was obtained by maxillary chilling and sumatriptan at posttreatment and 2 and 4 hours later. At 24 hours, some headache and nausea recurrence was noted with sumatriptan. The repeated-measures analysis of variance indicated that both treatments, drug (P = 0.024) and maxillary chilling (P = 0.001), reduced the headache, as compared with the control group. Tenderness suggests local inflammation associated with vasodilatation and edema. Because chilling can resolve local edema, these findings raise the possibility that an intraoral inflammation may be a factor in migraine etiology.

Gentamicin uptake in wild-type and aminoglycoside-resistant small-colony mutants of Staphylococcus aureus.

Gentamicin uptake and killing were studied in aminoglycoside-susceptible wild-type Staphylococcus aureus strains and aminoglycoside-resistant small-colony mutants selected by gentamicin from these strains. In wild-type S. aureus three phases of gentamicin accumulation were noted, and killing occurred during the last and most rapid phase of uptake. Uptake and killing were abolished by anaerobic growth and sodium azide, suggesting that energy-dependent active drug transport required respiration. Treatment of wild-type strains with the uncouplers N,N'-dicyclohexyl carbodiimide (DCCD) and carbonyl cyanide-m-chlorophenyl hydrazone showed disparate effects on gentamicin uptake, producing enhanced and diminished accumulations, respectively. Small-colony mutants demonstrated markedly deficient uptake compared with the wild-type strains and were not killed by gentamicin in concentrations up to 10 mug/ml. Several classes of aminoglycoside-resistant mutant strains are described. One mutant strain was a menadione auxotroph which, when grown in the presence of menadione, exhibited normal gentamicin uptake and killing. Gentamicin uptake and killing in this strain were abolished by KCN when the strain was grown in a medium supplemented with menadione. The membrane adenosine triphosphatase inhibitor DCCD was lethal for this mutant but not for other mutants or wild-type strains. Preincubation with menadione prevented the lethal effect of DCCD, and this strain demonstrated normal gentamicin accumulation when exposed to both DCCD and menadione. A second mutant strain demonstrated both gentamicin uptake and killing in the presence but not the absence of DCCD. Studies with small-colony mutants of S. aureus indicated that the defect in aminoglycoside uptake is very likely related to an inability to generate or maintain energized membranes from respiration. These studies suggest that the membrane energization associated with active aminoglycoside accumulation requires electron transport for the generation of a protonmotive force.