[Oral clarithromycin as a treatment option in chronic post-operative endophthalmitis]. / Claritromicina oral como opción terapéutica en endoftalmitis post-quirúrgicas tardías.

PURPOSE: To assess the outcome of medical treatment with oral clarithromycin in patients with chronic post-surgical endophthalmitis. METHODS: This prospective study was performed between January 1999 and September 2003. Patients with a diagnosis of chronic post-surgical endophthalmitis of bacterial etiology were included. All received 500 mg of oral clarithromycin twice a day for 14 days. The initial and final visual acuity, etiology, post-surgical time of presentation, treatment-delay time, and follow up were recorded. According to the treatment results, patients were distributed into 3 separate groups: 1) complete response, 2) partial response, 3) no response. Data from these groups were compared by means of the Student's t test and Fisher exact test, depending on which was considered most suitable. RESULTS: Fifteen cases of chronic endophthalmitis (11 of Propionibacterium acnes, 4 of Staphylococcus epidermidis) were diagnosed. A complete response was observed in 4 cases, partial response in 4 cases, and no response in 7 cases. Final visual acuity greater than 0.5 was significantly more likely in the complete response group when compared with the no response group (Fisher exact test = 0.0454, p=0.05), however, the same comparison between the complete response group and the partial response group was not significant. CONCLUSION: Medical treatment with oral clarithromycin could be useful in some patients with chronic post-surgical endophthalmitis.

Claritromicina oral como opción terapéutica en endoftalmitis post-quirúrgicas tardías / Oral clarithromycin as a treatment option in chronic post-operative endophthalmitis

Objetivos: Evaluar la respuesta al tratamiento médico con claritromicina oral de pacientes con endoftalmitis post-quirúrgica crónica.Métodos: Este estudio prospectivo se desarrolló durante el período comprendido entre enero de 1999 y septiembre de 2003. Se incluyeron pacientes con diagnóstico de endoftalmitis crónica de comienzo tardío que tuvieran etiología bacteriana. Se les administró claritromicina oral en 2 tomas diarias de 500 mg durante 14 días. Se registraron la agudeza visual inicial y final, la etiología, el tiempo de aparición del cuadro, el tiempo de demora de la instauración del tratamiento y el tiempo de seguimiento post tratamiento. Acorde a la respuesta al mismo los pacientes fueron distribuidos en 3 grupos: 1) Respuesta total, 2) respuesta parcial, 3) respuesta negativa.Las comparaciones estadísticas se realizaron mediante t de Student y la prueba exacta de Fisher según se consideró necesario.Resultados: Fueron diagnosticados 15 casos de endoftalmitis crónica (11 por Propionibacterium acnes y 4 por Staphylococcus epidermidis).Se observó respuesta total en 4 casos, parcial en 4 y negativa en 7.La comparación de las proporciones de pacientes con agudeza visual final mayor a 0,5 entre el grupo de respuesta total y el de respuesta negativa fue significativo (prueba exacta de Fisher= 0,0454 p=0,05). En cambio la misma comparación entre el grupo de respuesta total y el de respuesta parcial fue no significativo.Conclusiones: El tratamiento médico con claritromicina oral puede ser útil en algunos pacientes con endoftalmitis post-quirúrgica crónica

Purpose: To assess the outcome of medical treatment with oral clarithromycin in patients with chronic post-surgical endophthalmitis. Methods: This prospective study was performed between January 1999 and September 2003. Patients with a diagnosis of chronic post-surgical endophthalmitis of bacterial etiology were included. All received 500 mg of oral clarithromycin twice a day for 14 days. The initial and final visual acuity, etiology, post-surgical time of presentation, treatment-delay time, and follow up were recorded. According to the treatment results, patients were distributed into 3 separate groups: 1) complete response, 2) partial response, 3) no response. Data from these groups were compared by means of the Student’s t test and Fisher exact test, depending on which was considered most suitable. Results: Fifteen cases of chronic endophthalmitis (11 of Propionibacterium acnes, 4 of Staphylococcus epidermidis) were diagnosed. A complete response was observed in 4 cases, partial response in 4 cases, and no response in 7 cases. Final visual acuity greater than 0.5 was significantly more likely in the complete response group when compared with the no response group (Fisher exact test = 0.0454, p=0.05), however, the same comparison between the complete response group and the partial response group was not significant. Conclusion: Medical treatment with oral clarithromycin could be useful in some patients with chronic post-surgical endophthalmitis

Urinary and synovial pyridinium crosslink concentrations in patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVES: To assess urinary and synovial concentrations of hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to evaluate whether a combined measurement in the two compartments could give additional information about the origin of these compounds in joint diseases. METHODS: Concentrations of hydroxypyridinoline (HP) and lysylpyridinoline (LP) were measured by high pressure liquid chromatography in urinary and synovial samples collected from 20 patients with RA and 20 patients with knee OA. Full laboratory and clinical assessments were performed. RESULTS: Urinary concentrations of both HP and LP were significantly greater in RA than in OA. Urinary HP in RA correlated with the number of swollen joints corrected for Lansbury index and with erythrocyte sedimentation rate and C reactive protein. In synovial fluid from both groups, only relatively small amounts of HP were measured, while bone type I collagen specific LP was below the limit of detection in all samples. In RA patients, but not in OA patients, there was a strong correlation between urinary and synovial concentrations of HP (r = 0.75). CONCLUSIONS: The results underline the relationship between urinary HP and disease extent and activity in RA. The findings in synovial fluid support the hypothesis of an extraskeletal origin of HP in chronic joint diseases in which cartilage and synovial turnover may be increased.

Effect of salmon calcitonin on deoxypyridinoline (Dpyr) urinary excretion in healthy volunteers.

To evaluate the influence of synthetic salmon calcitonin (SMC) on bone resorption we investigated the modifications in urinary cross-links excretion [pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] induced by a single dose of the drug. The study was carried out in 16 healthy volunteers given a single dose of either 50 IU SMC I.M. or placebo, according to a double-blind, cross-over design. Urine was collected every 24 hours during the 72 hours after each treatment and Pyr and Dpyr were measured by an automated HPLC method. Pyr showed no significant difference after the two treatments, whereas in the first 24-hour urine collection Dpyr (nmol/24 hours +/- SD) was considerably lower after SMC than after placebo (118.9 +/- 26.0 against 147.2 +/- 45.0, P < 0.05). The amount of saved Dpyr was 19.2%. The selective effect of SMC on Dpyr excretion was more evident comparing the Pyr/Dpyr ratios for placebo and SMC during the first day of the study (4.1 +/- 0.6 against 4.8 +/- 0.7, respectively, P < 0.01). Using Eyre's formula (10 nmol Dpyr = 0.17 g bone) and assuming that no Dpyr is metabolized, the mean daily amount of bone resorbed was calculated (2.5 g for placebo and 2.0 g for SMC). The difference is the index of the bone-saving effect of SMC (0.48 g/day, or 19.2%). In conclusion, assuming that in healthy volunteers bone turnover is balanced with equal rates of formation and resorption, a dose of 50 IU I.M. of SMC reduces resorption, with a bone gain in the first 24 hours calculated as 9.4 mg/IU.

Characterization, regulation, and function of specific cell membrane receptors for insulin-like growth factor I on bone endothelial cells.

It is now widely accepted that insulin-like growth factor-I (IGF-I) has a local regulatory role in bone remodeling. IGF-I has also been demonstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF-I receptors and examined the effect of IGF-I on bone endothelium migration. Two classes of binding sites with high affinity for IGF-I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filtered conditioned media. Both IGF-I binding capacity and release decreased either with increases in cell number or after treatment with 17 beta-estradiol (17 beta E2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF-I. Taken together, these results strongly suggest that IGF-I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration.

Availability of synthetic salmon calcitonin in tissue fluid after a single intravenous dose.

To obtain further information about the availability of salmon calcitonin in the biophase compartment that surrounds the receptor site, salmon calcitonin concentrations in plasma and skin blister fluid (SBF) after a single i.v. dose of 100 IU synthetic salmon calcitonin were compared in 15 healthy volunteers. Serial blood and SBF samples were collected before and up to 8 h after administration and calcitonin was determined by a specific RIA. The maximum concentration in plasma was 225 pg.ml-1 (in the first sample at 15 min), whereas in SBF the mean peak of 84 pg.ml-1 was reached after about 30 min. The distribution of salmon calcitonin into SBF, defined as the ratio of the AUCs in SBF and plasma, was 1.5. The kinetic profiles of salmon calcitonin in plasma and interstitial fluid were different. Calcitonin in plasma peaked and then levelled out, while in SBF it persisted longer than in plasma. This is the first report of the distribution of salmon calcitonin into blister fluid.

Monitoring of free and total urinary pyridinoline and deoxypyridinoline in healthy volunteers: sample relationships between 24-h and fasting early morning urine concentrations.

Twelve healthy adults, six men and six women, with no history of bone or joint disease, were studied. They provided 24-h urine samples once weekly, five times, and a 24-h collection including the first sample of the early morning urine (FU). The urinary concentrations of free and total pyridinoline (HP) and deoxypyridinoline (LP), measured during the experimental period, showed no remarkable changes and gave good statistical correlations, particularly LP. Thus, in order to simplify and shorten the analytical procedure and the collection of biological samples, the only measurement of free fraction of HP and LP excreted in FU sample urine could be justified for both diagnostic and epidemiological purposes.

Antinociceptive activity of salmon calcitonin: electrophysiological correlates in a rat chronic pain model.

Experimental and clinical evidence testifies to an antinociceptive action of salmon calcitonin (sCT), administered in different ways, on the central nervous system. These studies were performed almost exclusively in acute pain models. The purpose of the present study was to investigate the effects of sCT, injected directly into the lateral cerebral ventriculi, on the firing of single nociceptive thalamic neurons, detected by electrophysiological techniques in an experimental model of prolonged or chronic pain, such as rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of sCT (5, 10, 20, 40 micrograms, 5 microliters/i.c.v.) it was possible to observe correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose-effect relationship. In agreement with electrophysiological findings, preliminary data, obtained with a patch clamp technique, on depression of calcium fluxes through neuronal membrane, induced by sCT, oriented the attention to a direct action of sCT on CNS.

Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation.

The topical tolerability of an intranasal salmon calcitonin spray preparation, of the excipients alone and of sodium taurocholate has been studied by assessment of the mucociliary transport velocity (MTV) on the frog's palate. The rate of mucus transport was investigated in 3 groups of animals (Rana esculenta; 6 frogs per group) in basal conditions and after a challenge with a salmon calcitonin intranasal spray preparation, with the excipients and with sodium taurocholate, respectively. The salmon calcitonin intranasal spray preparation and the excipients did not affect the mucociliary transport velocity on the frog's palate. On the contrary, sodium taurocholate produced severe impairments in the mucociliary transport velocity and histological lesions of the epithelial layer of the frog's palate. The comparison among the mean values of the mucociliary transport velocity before and after treatments showed a significant difference between controls and sodium taurocholate groups (p less than 0.05) as well as among the groups treated with sodium taurocholate versus salmon calcitonin and versus the excipients alone of the calcitonin preparation (p less than 0.05). These findings provide evidence that the salmon calcitonin intranasal spray preparation tested in the present ex vivo model does not affect the mucociliary transport velocity in the frog's palate, while this is markedly affected by sodium taurocholate. The use of sodium taurocholate as a promoter of absorption in intranasal preparations should thus be reconsidered.

Roxithromycin disposition in tonsils after single and repeated administrations.

Levels of roxithromycin in serum and tissue were investigated in 29 subjects undergoing tonsillectomy. A total of 13 subjects received a single oral dose of 300 mg, and 16 received four oral doses 12 h apart as follows: a 300-mg loading dose followed by three 150-mg doses. Measurable levels of roxithromycin were present in tonsil samples of 11 of 13 subjects in the first group. The mean levels in tonsils and serum were 0.8 microgram/g and 6.7 micrograms/ml, resulting in a mean tissue/serum ratio of 0.16. In the multiple-dose group, roxithromycin was found in 14 of 16 subjects at mean levels in tonsils and serum of 1.6 micrograms/g and 8.7 micrograms/ml, and the tissue/serum ratio was 0.23.