Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes

 · Background: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. · Methods: Cataract patients (n=224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3×1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50–100 μl aqueous humor was aspirated and stored at –80 °C. The HPLC method was used for measuring the concentration. · Results: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8±327.8 μg/l (range 33–1388 μg/l), norfloxacin 182.1±118.1 μg/l (range 38–480 μg/l) and ofloxacin 563.9±372.1 μg/l (range 64–1455 μg/l). These mean concentration are all above the MIC₉₀ of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC₉₀ of Staphylococcus aureus and Staphylococcus epidermidis · Conclusions: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC₉₀ values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa. Received: 8 September 1997 Revised version received: 19 March 1998 Accepted: 8 April 1998     

Nonsteroidal Anti-Inflammatory Drugs and Prostaglandins: Their Interactions and Effects on the Particulate-Induced Inflammatory Process Implicated in Joint Implant-Loosening and on Monosodium Urate Crystal-Induced Inflammation

The objective of this study was to determine the effects of orally administered misoprostol and diclofenac on inflammation caused by particulates in the rat subcutaneous air-pouch model. Subcutaneous air pouches were formed in male Sprague-Dawley rats. The animals were premedicated by gavage with either saline, diclofenac, misoprostol, or both diclofenac and misoprostol. The air pouches were injected with either polymethyl methacrylate particles or monosodium urate crystals, and the pouch fluids were obtained at 1, 6, 24, 48, and 72 h. Leukocyte influx, tumor necrosis factor, neutral metalloprotease activity, and prostaglandin E(2) levels were measured. It was determined that leukocyte influx was inhibited by diclofenac in the acute inflammation caused by monosodium urate crystals only. In all animals receiving diclofenac, prostaglandin E(2) (PGE(2)) levels were reduced, whereas tumor necrosis factor levels were elevated. The elevation of tumor necrosis factor was prevented by the addition of misoprostol. It is concluded that the oral administration of diclofenac or misoprostol can affect levels of specific mediators involved in particulate-induced inflammation in the subcutaneous air pouch.     

Intraocular silicone lenses in silicone oil: an experimental study

Background: To evaluate a potential effect of silicone oil on flexible silicone intraocular lenses, four lenses (STAAR AA-4203) were stored in silicone oil under sterile conditions for periods between 1 month and 3 years. Method: The edge and surface of the lenses were examined by scanning electron micrography and the findings compared with a lens of the same model which had been stored in Ringer's solution for 2 years. Results: After 1 year of silicone oil exposure, droplets of different sizes adherent to the surface of the lens were found. These changes proceeded to a wave-like appearance of the surface after 2 and 3 years of storage, so that a continuous layer of silicone oil polymers is probably covering the intraocular lens. Conclusion: Optical interference has to be considered a possibility if it turns out that the droplets cannot be removed during silicone oil evacuation. Consequently silicone intraocular lenses without hydrophilic preparation of the surface should not be implanted in eyes undergoing combined anterior and posterior segment surgery with silicone oil tamponade or in eyes with high risk for vitreoretinal complications.The authors state that they have no proprietary interest in the marketing of the products mentioned herein or competing products     

Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography

Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure - emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed yttrium-86 as a substitute for⁹⁰Y, with detection by positron emission tomography (PET). The study compared the properties of two different⁸⁶Y complexes —⁸⁶y-citrate and⁸⁶Y -ethylene diamine tetramethylene phosphonate (EDTMP) — in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the⁸⁶Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing⁹⁰Y. In 1 cm³ of bone metastasis, doses of 26±11 mGy/MBq and 18±2 mGy/MBq were determined per MBq of injected⁹⁰Y- citrate and⁹⁰Y- EDTMP, respectively. The doses to the bone marrow were 2.5±0.4 mGy/MBq for⁹⁰Y- citrate and 1.8±0.6 mGy/MBq for⁹⁰Y-EDTMP.⁸⁶Y and PET provide quantitative information applicable to the clinical use of⁹⁰Y. This method may also be useful for the design of other⁹⁰Y radiopharmaceuticals and for planning radiotherapy dosages.     

Die lokalisierte Form einer sympathischen Reflexdystrophie

Introduction

The reflex sympathetic dystrophy (RSD) syndrome usually shows a distally generalized distribution pattern of symptoms. Here we report a case with a distally localized form of RSD.

Patient and methods

In a 53-year-old woman, following a local lesion in the nail bed of the left thumb, a neuroma developed at the side of the lesion during the next half year. She was finally operated upon. Following that intervention, a complex and painful clinical syndrome occurred that for the most part affected only the thumb. A clinical neurological examination was carried out, including distal suprasystolic compression of the affected extremity after bandaging it (the so-called ischemia test). For diagnostic and therapeutic reasons, afterwards a conventional blockade of the ipsilateral stellate ganglion was applied.

Results

The clinical investigation showed a triad of autonomic (swelling, side difference of skin temperature, hyperhydrosis), motor (reduced movement ability, tremor) and sensory disturbances (spontaneous pain, allodynia), which nearly exclusively affected the entire left thumb. The spontaneous pain showed an orthostatic component (the pain being diminished or exaggerated when the extremity was elevated or lowered, respectively) and was suppressed by the ischemia test. Following the sympathetic block, all symptoms disappeared within one day (follow-up period: 5 months).

Conclusion

In contrast to the common clinical picture of RSD, with a distally generalized distribution of symptoms, the present case showed a so-called localized form of RSD, its triad affecting only the thumb with the lesion. Typically, the pain showed an orthostatic component and was suppressed by the ischemia test. The sympathetic block was immediately successful, proving the occurrence of this form of RSD for the first time. In similar clinical cases, this form of RSD should be considered as a differential diagnosis.     

Using pharmacokinetics in drug therapy III: Estimating dosage regimens and blood levels using the fraction-lost method

The "fraction of drug lost during dosage interval" method, which yields rapid estimates for drug dosage regimens and blood levels, is described. Estimation of the fraction lost during a dosage interval allows further calculation of dosage regimens and steady-state blood levels. The estimates derived from this method are valid only when the pharmacokinetics of the drug are linear and elimination from the body occurs according to first-order kinetics. Other limitations of the method are discussed.     

Bogengeführte Zahnbewegung — Dynamik,Effektivität und Nebenwirkungen

Zusammenfassung Im Rahmen der vorliegenden Studie werden die Einflüsse der Parameter Drahtdimension (Rund- oder Kantdraht), krafterzeugendes Element (elastische Kette, Zugfeder, Zugfeder am Powerhook, Zugfeder mit Aufrichtefeder), Bracket (schmal, breit) und Lage des Wderstandszentrums auf die Bewegungseffektivität und Nivellierungsverluste (Kippung, Rotation, Extrusion) bei der bogengeführten Eckzahnretraktion untersucht. Neben Messungen am Stahldraht wurden vergleichsweise auch verseilte Drähte und Nickel-Titan-Drähte einbezogen. Die Simulation der Bewegung erfolgte mit Hilfe des orthodontischen Meßund Simulationssystems (OMSS). Die für das 0,018-Inch-Slotsystem ermittelten Ergebnisse bestätigen das allgemein übliche klinische Vorgehen der Eckzahndistalisation an einem 0,016×0,022-Inch-Vierkantstahlbogen, solange man mit der bogengeführten Technik arbeitet. Empfehlenswert ist der Einsatz einer Nickel-Titan-Zugfeder. Durch ihre relativ konstante Kraft über einen großen Aktivierungsbereich ermöglicht sie eine effektivere Distalisierung als eine elastische Kette. Bei Anwendung eines Powerhook bzw. einer Aufrichtefeder lassen sich Nivellierungsverluste weitgehend vermeiden und somit eine körperliche Bewegung am ehesten garantieren. Der Distalisierungseffekt wird dabei jedoch nur unwesentlich verstärkt. Die Gefahr eines zu groß gewählten Antitipmomentes ist streng zu beachten. Einen deutlichen Einfluß auf die Bewegungseffizienz zeigt die Lage des Widerstandszentrums. Je weiter apikal das Widerstandszentrum lokalisiert ist, wie beispielsweise bei einer längeren Zahnwurzel, desto geringer erweist sich die Distalisierungseffektivität. Gute Ergebnisse in bezug auf die Effizienz der Distalisierung wurden in Verbindung mit einem verseilten Bogen ermittelt. Seine Anwendung ist jedoch wegen zu starker Nivellierungsverluste in der Führungsphase abzulehnen.

---

Summary Canine retraction on a continuous arch wire was simulated using the OMSS. The influence of wire dimension, force generating element (power chain, coil spring, powerhook, uprighting spring), bracket width and the position of the center of resistance on the effectiveness of the distalization of the canine and its side effects such as extrusion, rotation and tipping were examined. Stainless steel, nickel titanium and multistranded wires were tested. Employing the 0.018-slot system, the use of an 0.016×0.022-arch wire gave the best results. Comparing the NiTi coil spring with the elastic chain, the former should be preferred, because, due to its low load deflection it generates a nearly constant force over a wide range of activation. Using powerhooks or uprighting springs, a nearly bodily movement could be achieved. On the other hand, friction may increase if the uprighting is too strong. The rate of tooth movement decreases by increasing length of tooth root represented by the position of the center of resistance. Arch guided tooth movement along multi-stranded wires shows a high effectiveness, nevertheless, these wires should not be used for canine retraction because of the above mentioned side effects.

---

---

Herrn Professor Dr. Dr.G. P. F. Schmuth zum 65. Geburtstag.

---

Diese Arbeit wurde zum Teil gefördert durch die Deutsche Forschungsgemeinschaft (Dr 196/1).     

The combined treatment of preimplantation mouse embryos in vitro with cadmium (CdSO4, CdF2) and X-rays

The influence of cadmium (up to 10^?4 M), fluoride (up to 10^?4 M), and X-rays (up to 18.8 Gy) on different variables of preimplantation mouse embryos in vitro has been examined. The agents were applied either singly or in combination (0.94 Gy X-rays +3×10^?7 M CdSO₄ or CdF₂; 0.94 Gy X-rays +3×10^?6 M CdSO₄ or CdF₂). The following variables were determined:

1. the microscopic visible development until 144 h post conceptionem (=144 h p.c.),
2. the average cell numbers (48 h p.c., 56 h p.c., 72 h p.c., 96 h p.c., 120 h p.c., 144 h p.c.),
3. the number of micronuclei (72 h p.c.),
4. the distribution of cell nuclei within the cell cycle (72 h p.c.).

Nearly all results of the combination experiments correspond to the sum of the single effects. Only two values (out of about 40) significantly exceed the value obtained after addition of the single effects; both values lie within the envelope of additivity.     

A new variety of "empty sella" with cystic intrasellar dilatation of the recessus infundibuli.

A new variety of the "empty sella" consisting of polycystic intrasellar dilatation of the infundibular recess is described. The underlying embryonal developmental anomaly of the pituitary gland and diaphragma sellae and the possible effect of increased intracranial pressure are discussed and the malformation is compared with embryonal stages of ventricular development.