Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.     

Brainstem auditory evoked responses in patients with tinnitus

Brainstem auditory evoked responses of 355 patients with uni- or bilateral tinnitus were recorded in order to evaluate the effect of tinnitus on the central auditory system. The amplitudes of waves I, III and V and the latencies of each wave and interpeak latencies were compared to those of a group of 129 controls with normal hearing. The study of the control group initially identified a certain number of concurrent parameters. The brainstem evoked responses of men and women evolved differently from the age of 30 years, latencies of I-III and I-V in men lengthening with age and those of women tending to shorten. The patient groups were therefore compared to a control group of the same sex ratio or of the same sex, half being between 30 and 56 years of age. The tinnitus patients were divided into three groups according to the side affected by tinnitus. Latencies and amplitudes in these groups differed significantly from those of the control group. In order to eliminate hearing loss, the most difficult concurrent factor and almost always associated with tinnitus, the results of individuals with symmetrical hearing loss were compared to those of the control group. Tinnitus was always associated with significant lengthening of 0-I and I-V latencies on the tinnitus-affected side, with a significant reduction in amplitudes of waves I and III, and sometimes of wave V, particularly in the group with left-sided tinnitus. Comparison of tinnitus patients with symmetrical and asymmetrical hearing by sex showed that tinnitus patients of all groups had lengthening of right and left 0-I latencies, apart from the women in the group with right-sided tinnitus, and significant reduction in amplitudes of waves I and III in women and of left III only in men. When hearing loss was asymmetrical and on the tinnitus-affected side, there was also lengthening of 0-I latencies on the tinnitus-affected side in both sexes and of ipsi- and contralateral I-V latencies in women. Right- and left-sided tinnitus was associated with additional differences between the three groups. Correlation coefficient study confirmed that 0-I, I- III and I-V latencies were independent of the mean degree of deafness, deafness at high frequencies and at frequencies around the tinnitus, up to a threshold of hearing loss of 40 dB, above which 0-I and 0-V lengthened in addition to tinnitus. On the other hand, whatever the frequency, tinnitus involved significant lengthening of wave I latencies and modification of the previously recorded amplitudes. Two groups of tinnitus patients could be distinguished: the first, with symmetrical hearing loss, with symmetrical normal latencies, apart from 0-I latencies and the amplitude of the wave on the tinnitus side, and the second with hearing loss predominant on the tinnitus-affected side, with different latencies on each side, 0-I being shorter on the unaffected side, I-III and I-V being lengthened on the unaffected side and 0-I being lengthened on the tinnitus-affected side. Moreover, as disturbances of brainstem evoked responses caused by tinnitus particularly affected waves I and III, the hypothesis of possible involvement of the efferent systems could be proposed.     

Use of Mono Mac 6 human monocytic cell line and J774 murine macrophage cell line in parallel antimycobacterial drug studies

The Mono Mac 6 (MM6) human monocytic cell line was evaluated with the established J774 murine macrophage cell line to ascertain its effectiveness in determining the intracellular activities of antimycobacterial drugs. Cells were infected with Mycobacterium tuberculosis H37Ra and treated with drug concentrations corresponding to the MICs, as well as to threefold higher than and threefold less than the MICs. Changes in CFU were compared after 7 days to determine significant differences between treated and nontreated groups. The results suggest that MM6 will make a useful model for testing the intracellular activities of antituberculosis drugs.     

The measurement of gastric motor function and transit in man by echo planar magnetic resonance imaging

Echo-planar imaging (EPI) can be used to produce snapshot images of the human stomach and antro-pyloro-duodenal segment in real time as an alternative technique to intubation and exposure to ionizing radiation. The method has been further developed to monitor simultaneous gastric motility and gastric emptying of liquid and solid meals. The model has been utilized to study the effects of pharmacological agents on gastric function.Eight normal subjects were imaged in a 0.5-T superconducting magnet for up to 6 h following ingestion of 800 ml tap water, followed by 500 ml porridge test meal + 500 ml tap water. A rapid multislice technique was adopted to image adjacent transverse slices (10 mm thick) through the gastric region. In addition, three subjects were orally dosed with 20 mg of the prokinetic agent Cisapride. Gastric volumes for each slice were calculated and summed to produce a measure of total gastric volume and gastric emptying. Contractile activity at the level of the antro-pyloric segment was detected using sequential 128 ms images at 3 s intervals. Alternate measurements of gastric volume and motility were made for the duration of the study.Gastric emptyingT _1/2's (times to empty 50% of the gastric contents) of 12.9 min for water and 116 min for porridge were in agreement with results obtained by the traditional techniques of gamma scintigraphy and impedance imaging. The frequency of gastric contractions increased from 2.4 contractions per minute (cpm) to 3.2 cpm following water and from 2.9 to 3.2 cpm following porridge. The prokinetic effect of enhanced coordination of antroduodenal contractions was also observed. These studies have demonstrated that EPI can be used to detect and image gastroduodenal function in man, totally noninvasively, and can be used to study the effects of drugs acting on the gastrointestinal tract.     

The effect of high temperature plastic flow on the superconducting transition in A15 compounds

Low temperature heat capacity measurements have been made on hot isostatically pressed Nb₃Sn and arc cast, homogenized, and A15 transformation annealed V-23.3 at. pct Ga and V-18.1 at. pct Ga. The heat capacity measurements display the superconducting transition temperature (T _c), and have been used to evaluate the effects of plastic deformation on theT _c range. Plastic deformation to the extent of 15 pct compression at 1525 and 1650 °C does not alter the superconducting transition in polycrystalline Nb₃Sn. Plastic deformation to the extent of 15 pct compression at 1050 and 1200 °C does not alter the superconducting transition in polycrystalline V-23.3Ga, transformed to A15 structure with a fifty-hour 1150 °C anneal. The same statement can be made for A15 V-18.1Ga, deformed at 1050 °C after a fifty-hour, 1150 °C anneal. With onlyfive hours annealing at 1150 °C, A15 V-23.2Ga displays a lowering and broadening of theT _c range upon 1050 and 1200 °C plastic deformation. With onlyfive hours annealing at 1150 °C, A15 V-18.1Ga displays a broad, but increasedT _c range after plastic deformation at 1050 °C.     

Two-degree-of-freedom output feedback controllers for discrete-time nonlinear systems

A discrete-time, model-based output feedback control structure for nonlinear processes is developed in the present work. The structure makes use of a closed-loop observer, while at the same time it guarantees that the overall feedback controller possesses integral action. An algebraic transformation is applied on the observer states to insure that the input/output gain of the observer matches the model upon which the static state feedback control law is based. The resulting control algorithm is a two-degree-of-freedom control law, in the sense that the output and the set point are processed in different ways. The control structure is shown not only to have the same properties as the standard model-state feedback structure, but also that it emerges from a model algorithmic control framework. Finally, a simulation example using an exothermic CSTR operating at an open-loop unstable steady state is used to evaluate the closed-loop performance of the proposed method.     

Comparing the power of linkage detection by the transmission disequilibrium test and the identity-by-descent test

The purpose of this study was to identify new trends in the changing indications for penetrating keratoplasty. We retrospectively reviewed the clinical and pathologic diagnoses of 1,104 corneal buttons that had been submitted to the Estelle Doheny Eye Pathology Laboratory, Los Angeles, during the 5-year period 1989-1993. The leading indications, in order of decreasing frequency, were pseudophakic corneal edema (24.8%), regrafts (21.3%), scarring with or without chronic inflammation (11.1%), keratoconus (7.1%), aphakic corneal edema (6.4%), and ulcerative conditions (5.8%). The incidence of pseudophakic corneal edema remained stable over the study period and was actually surpassed by regraft in the last year of the study. Although pseudophakic corneal edema remains the predominant indication for penetrating keratoplasty, our findings suggest that its occurrence rate has begun to level off.