Effect of inoculum size on the induction of endophthalmitis in aphakic rabbit eyes

A reproducible animal model is necessary to examine the use of antimicrobial agents for prophylaxis and treatment of bacterial endophthalmitis. We determined the minimum inoculum size of S. aureus and P. aeruginosa that consistently produced endophthalmitis when injected into aphakic rabbit eyes immediately following surgery. Both anterior chamber and intravitreal injections were examined. For S. aureus, an intravitreal inoculum of 19.3 +/- 7.5 CFU and an anterior chamber inoculum of 50.5 +/- 4.0 CFU were required. For P. aeruginosa, an intravitreal inoculum of 5.5 +/- 2.6 CFU and an anterior chamber inoculum of 97.5 +/- 10.7 CFU consistently produced a fulminant infection. Lower inocula of both bacteria produced endophthalmitis in both locations, but the effect was inconsistent.     

Use of the Radionics Image Fusiontrade mark and Stereoplantrade mark programs for target localization in functional neurosurgery

We describe the use of Radionics Image Fusiontrade mark and Stereoplantrade mark in defining the target for thalamotomy and pallidotomy in functional surgery for parkinsonism and tremor. Using this to fuse and spatially correct magnetic resonance imaging (MRI) to computed tomography (CT) images our calculated targets were a mean of 0.6 +/- 1.5 mm from the end target determined physiologically by stimulation. This is significantly better than the values of 2.6 +/- 1.6 mm for thalamic targets and 7.1 +/- 3.7 mm for pallidal targets using CT alone. As a consequence, determination of the target and the lesion making are routinely performed in one pass of the electrode allowing for faster, more accurate and, we believe, safer functional procedures.     

CT-guided thalamotomy in the treatment of movement disorders

CT-guided thalamotomy has been used in Frenchay Hospital since 1985 in the treatment of movement disorders. This technique avoids intraventricular contrast injections and therefore simplifies the placement of thalamic lesions, decreases patient morbidity and shortens inpatient stay. Our experience with this technique is presented.     

Reduced Systemic Availability of an Antiarrhythmic Drug,Bidisomide, with Meal Co-administration: Relationship with Region-Dependent Intestinal Absorption

Purpose. The aim of this research was to determine the mechanism by which a co-administered meal decreases the oral absorption of bidisomide and does not influence the oral absorption of the chemically-related antiarrhythmic agent, disopyramide. Methods. Bidisomide plasma levels, following oral administration and intravenous infusion in the fasted state and with various meal treatments, were determined in human subjects. A dialysis technique was employed to examine the potential for drug binding to meal homogenates. Plasma levels, following drug administration through duodenal and jejunal intestinal access ports and following various meal treatments with oral drug co-administration, were compared for bidisomide and disopyramide in a canine model. Results. Bidisomide plasma AUC was significantly reduced following oral drug co-administration with breakfast compared to fasted-state controls in human subjects and in dogs independent of the composition of the solid cooked breakfast. While intravenous bidisomide infusion in human subjects showed a statistically significant reduction in AUC 15 minutes after oral administration of a high fat breakfast as compared to drug infusion in the fasted state, the reduction (–13%) was substantially smaller than the reduction (from –43% to –63%) observed with oral bidisomide meal co-administration. The percentages of bidisomide and disopyramide lost by binding to homogenates of cooked breakfast were 25.0 ± 5.7% and 23.7 ± 7.7%, respectively, as determined by dialysis at 4 hours. In dogs, the extent of absorption of disopyramide was comparable from oral, duodenal and mid-jejunal administration while the extent of bidisomide absorption from mid-jejunal administration was significantly lower than for oral or duodenal administration. Non-viscous liquid meals decreased C_max but not AUC, while viscous homogenized solid meals decreased both C_max and AUC for bidisomide with oral drug-meal co-administration. Oral non-caloric hydroxypropyl methylcellulose meals decreased bidisomide to the same extent as homogenized solid meals but did not lower disopyramide AUC. Conclusions. The significant reduction in bidisomide plasma levels observed with meal co-administration in human subjects was predominantly mediated through a reduction in drug absorption and was independent of solid meal composition. The difference in meal effect on the absorption of the two drugs in humans did not appear to be a function of drug binding to cooked meal components over typical human upper gastrointestinal residence times. In dogs, the high-viscosity medium generated by oral co-administration of a solid meal reduced the upper intestinal absorption of bidisomide and disopyramide. Bidisomide AUC was decreased since it was well absorbed in the upper but not lower small intestine. Disopyramide AUC was not significantly affected since it was well absorbed from both regions. A similar mechanism may play a role in drug plasma level reductions following oral co-administration with solid meals for drugs showing similar regionally-dependent absorption profiles.     

Treatment of advanced transitional cell carcinoma of the bladder with irradiation and concomitant 5-fluorouracil infusion

Twenty patients with advanced transitional cell carcinoma of the bladder were treated with radiation and concomitant continuous infusion of 5-fluorouracil with or without Mitomycin. Nineteen of 20 patients were assessed for response. Fourteen of 19 patients (74%) obtained a complete response within 3 to 6 months. An additional three patients (15%) acquired and maintained a complete response after local transurethral resection of the tumor and intravesical chemotherapy, raising the overall complete response (CR) rate to 17/19 (89%). Of the two patients with persistent disease, one is alive and well after salvage cystectomy. Eighteen of 20 patients were evaluated for survival with a median follow-up of 38 months. Seven patients remain alive and well 51 to 78 months, whereas three patients died from intercurrent disease. Eight patients died of either distant metastatic disease (7 patients) or regional disease (1 patient). An adjusted survival calculated by the Life Table Method was 53.6% at 5 years, whereas the overall survival was 39%. The combined modality therapy was well tolerated with no need for treatment interruption or reduction in dose. Late bladder complications include one patient with hemorrhagic cystitis, two patients with dysuria, and two with symptoms of irritable bladder. One patient required a colostomy for a chronic hemorrhagic proctitis. Bladder preservation was achieved in 19/20 patients.     

Effect of single-dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement.

Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.     

Bilateral breast carcinoma: 28 years' experience

From 1959 to 1987, a total of 1,182 histologically proven breast cancer patients were followed. Of these, 48 (4.06%) with bilateral breast carcinoma were reviewed. Eight patients (0.68%) had simultaneous breast carcinomas and the remaining 40 (3.38%) had nonsimultaneous breast carcinomas. The period between the development of the first and second primary carcinoma ranged from 17 to 200 months (mean, 86 months). The second primary carcinoma was found symetrically located with the first primary carcinoma in only 34.5% of the cases. No significant differences were observed between the bilateral carcinoma patients and the unilateral carcinoma patients with respect to pregnancy, delivery, family history, and the size and localization of the carcinomas. Axillary metastasis was seen in a higher percentage of the second primary carcinomas (48% versus 37.5%). It was observed that the shorter the time interval between the presentation of the carcinomas, the shorter the survival.

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Resumen Entre los años 1959 y 1987, un total de 1,182 pacientes con cancer mamario comprobado histológicamente fueron seguidas. De éstas, 48 (4.06%) presentaron carcinoma mamario bilateral y son el objeto de esta revisión; 8 (0.68%) lo presentaron simultáneamente y las otras 40 (3.38%) no simultáneamente. El período entre el desarrollo del primero y el segundo carcinoma primario varió entre 17 y 200 meses (promedio, 86 meses). El segundo carcinoma primario fue hallado simétricamente ubicado en relación al primero en sólo 34.5% de los casos. No se encontraron diferencias significativas entre las pacientes con carcinoma bilateral y los que presentaron carcinoma unilateral con relación a embarazos, partos historia familiar o tamaño y ubicación de los carcinomas. Se registraron metástasis axilares en un mayor porcentaje en los segundos carcinomas primarios (48% versus 37.5%). Se observó que entre más corto el intervalo entre la presentación de uno y otro carcinoma, más corta la supervivencia.

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Résumé Nous avons suivi de 1959 à 1987 1,182 patientes ayant un cancer du sein histologiquement prouvé. Nous en avons revu 48 (4.06%) ayant un cancer du sein bilatéral. Huit patientes (0.68%) avaient un cancer du sein bilatéral simultané et les 40 autres (3.38%) un cancer du sein bilatéral dont le deuxième était découvert entre 17 à 200 mois (moyenne, 86 mois) après le premier. Le second cancer primitif était symétrique au premier cancer primitif dans 34.5% des cas seulement. Nous n'avons pas observé de différence significative entre les patientes ayant un cancer bilatéral et celles qui avaient un cancer unilatéral en ce qui concerne grossesse, accouchement, antécédent familiaux, et taille et localisation des cancers. Nous avons observé un pourcentage plus fort de métastases axillaires des deuxièmes cancers primitifs (48% pour 37.5%). Nous avons constaté que plus était court l'intervalle entre l'apparition des cancers plus était courte la survie.

     

The chemotherapy of onchocerciasis X. An assessment of four single dose treatment regimes of MK-933 (ivermectin) in human onchocerciasis

Nineteen patients from an area of vector control in the savanna region of Northern Ghana, all with moderate to heavy infections with Onchocerca volvulus and some with ocular involvement, were treated with 50, 100, 150 or 200 micrograms kg-1 of ivermectin. Detailed monitoring of clinical and ocular reactions and of alterations in skin microfilarial counts and laboratory indices were carried out during the first 28 days. Microfilarial counts in skin snips and detailed ocular examinations were then repeated at intervals over a period of nine months. Ivermectin slowly eliminated microfilariae from the skin and eye without serious adverse clinical or ocular reactions in all treated groups. There was little difference in efficacy between doses of 100, 150 and 200 micrograms kg-1, and these were more effective than the 50 micrograms kg-1 dose. Very low levels of skin microfilariae were maintained for nine months. Microfilariae were not eliminated from the eye for at least three months. The drug was neither macrofilaricidal nor embryotoxic. However, it produced a dose-dependent stimulation of embryogenesis manifest at one month and succeeded by a suppression of embryogenesis at three months after therapy. In areas where transmission of onchocerciasis has been interrupted, ivermectin may need not be given more often than once a year. The efficacy of the drug on single dosage and the mild adverse reactions produced, if confirmed in subsequent controlled studies, would greatly simplify the treatment of onchocerciasis and would reintroduce new concepts of the role of chemotherapy in the control of onchocerciasis.