Penetration of moxifloxacin into the human aqueous humour after oral administration.

AIMS: To determine the pharmacokinetics of moxifloxacin, a new generation fluoroquinolone, in the anterior chamber of the human uninflamed eye. METHODS: 35 patients undergoing cataract surgery received two doses of 400 mg of oral moxifloxacin with a 12 hour interval and were divided into six groups. Moxifloxacin levels in aqueous humour and serum were determined by a microbiological agar well diffusion technique at 2, 4, 6, 8, 10, and 12 hours after the second dose in each group respectively. RESULTS: Mean moxifloxacin levels in the anterior chamber were 1.20 (SD 0.35) microg/ml at the 2 hours group, 1.22 (0.48) microg/ml at the 4 hours group, 1.20 (0.45) microg/ml at the 6 hours group, 1.58 (0.38) microg/ml at the 8 hours group, 1.37 (0.44) microg/ml at the 10 hours group, and 1.23 (0.55) microg/ml at the 12 hours group. The mean ratio of aqueous to serum moxifloxacin level was 38%. CONCLUSION: Moxifloxacin penetrates well into the anterior chamber of the human uninflamed eye after oral administration, reaching early significant levels, which are maintained for at least 12 hours and are much higher than the MIC(90) values of Gram positive and Gram negative pathogens commonly implicated in intraocular infections with the exceptions of fluoroquinolone resistant staphylococci, MRSA, and Pseudomonas aeruginosa.

The effect of acetazolamide on the kinetics of four newer beta-lactams in the aqueous humor.

OBJECTIVE: To evaluate whether the effect of acetazolamide on piperacillin's aqueous humor concentrations observed in animals exists also in humans for ceftazidime, cefotaxime, ceftriaxone and aztreonam. METHODS: One hundred and eighty-eight patients undergoing eye cataract surgery were randomly allocated to receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with (subgroup A) or without (subgroup B) concomitant oral administration of acetazolamide. Antibiotic concentrations in serum and the aqueous humor, simultaneously sampled during the operation, were measured using an agar well diffusion technique, and the ratios of the concentrations of aqueous humor to serum were calculated and compared. Statistical analysis was performed by using the paired t-test. RESULTS: Mean aqueous humor ceftazidime concentrations at 2, 4 and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L (subgroup B). Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77 mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam 6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B). Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41 mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B). The differences in aqueous humor concentrations when acetazolamide was administered were statistically significant (P < 0.05), with the exception of ceftazidime 6 h, cefotaxime 6 h and ceftriaxone 2 h. CONCLUSIONS: Although acetazolamide resulted in statistically significant increases in the aqueous humor concentrations of all the antibiotics tested, this effect was most marked for ceftazidime.

Vancomycin levels in human aqueous humour after intravenous and subconjunctival administration.

The purpose of the present study was to evaluate the level of vancomycin in human aqueous humour after intravenous (i.v.) and subconjunctival administration. One hundred patients scheduled to undergo cataract extraction participated in the study. Fifty-three of them received 20 mg vancomycin subconjunctivally and 47 received two doses of vancomycin i.v. (1 g b.i.d.). Specimens of aqueous humour from the first group were collected 1, 2, 2.5, 3, 3.5, 5, 6, 7, and 8 h after the subconjunctival injection. In the second group, specimens of blood and aqueous humour were collected 1, 2, 4, 6, 8, 10, and 12 h after the end of infusion of the second dose of the antibiotic. The levels of vancomycin were determined by fluorescent polarization immunoassay. In the first group peak levels of 24.82+/-3.55 microg/ml were achieved in aqueous humour at 5 h, whereas in the second group peak levels of 1.42+/-0.47 microg/ml were detected at 6 h. The latter levels, although higher than the MICs of most of the Gram-positive pathogens causing eye infections, are inadequate for the treatment of infections in vivo. These results support the need for subconjunctival instead of i.v. administration of vancomycin in order to achieve therapeutic levels of the drug in human aqueous humour or for prophylactic use whenever indicated.

Angioid streaks in homozygous beta thalassemia.

One hundred patients with homozygous beta thalassemia (62 had beta thalassemia major and 38 had beta thalassemia intermedia) were examined by ophthalmoscopy for angioid streaks. Angioid streaks were found in 20 patients from both the beta thalassemia major and beta thalassemia intermedia groups (nine and 11 patients, respectively). A positive correlation was found between age and angioid streaks (P = .0017), as was a difference in the prevalence of angioid streaks between the two forms of the disease (P = .079). Additionally, a significant correlation was noted between chelating therapy and the prevalence of angioid streaks (P = .039). However, using multivariate analysis to correct for the effects of age, the correlation of angioid streaks with the form of disease disappeared, whereas the level of significance between chelation therapy and angioid streaks was reduced (P = .05). The high frequency of angioid streaks observed in patients with beta thalassemia and the severe complications observed in one patient render a thorough ophthalmoscopic examination and follow-up of such patients necessary for both early diagnosis and possible therapeutic intervention.

Angioid streaks in sickle-thalassemia.

Angioid streaks have been described in a diverse group of diseases including hemoglobinopathies such as sickle cell anemia and beta-thalassemia. We investigated the prevalence of angioid streaks and pseudoxanthoma elasticum in the rare situation of patients who had compound heterozygous traits for hemoglobin S and beta-thalassemia. We examined 58 consecutive patients with sickle-thalassemia. Of these, 25 were men and 33 were women, and they ranged in age from 19 to 58 years (mean, 32.6 years). Angioid streaks were identified in six of 58 patients (10%), and of these three also displayed the cutaneous lesions of pseudoxanthoma elasticum, which were confirmed by skin biopsy. An expanded study on several relatives of the patients with angioid streaks failed to identify any similar cases. Statistical evaluation of the main hematologic and biochemical parameters in the patients with and without angioid streaks did not demonstrate any significant differences, except that the thalassemic component in all six patients with angioid streaks was beta(0) (that is, did not allow the synthesis of hemoglobin A). We conclude that angioid streaks and pseudoxanthoma elasticum skin lesions occur with an increased frequency in patients with sickle-thalassemia.

Lack of response to corticosteroids and pulse cyclophosphamide therapy in Cogan's syndrome.

A 17-year-old girl with Cogan's syndrome is described. Total and irreversible hearing loss occurred which was unresponsive to corticosteroids and immunosuppressive therapy. The girl died a year later from subarachnoid haemorrhage. The lethal prognosis in Cogan's syndrome despite the available treatment is emphasized.

Arterial calcifications in beta-thalassemia.

The purpose of this study was to define the incidence of arterial calcifications in patients with beta-thalassemia. Beta-thalassemia patients have been shown to present a high prevalence of angioid streaks and skin lesions characteristic of pseudoxanthoma elasticum (PXE). Given the fact that vascular involvement in the form of arterial calcifications is also a common manifestation of PXE, the authors investigated radiographically the presence of arterial calcifications in beta-thalassemia patients. They studied 40 patients with beta-thalassemia over 30 years of age. Forty healthy, age- and sex-matched subjects were chosen as a control group. Radiographs of the tibias were performed in order to disclose arterial calcifications. The occurrence of PXE skin lesions and of angioid streaks (AS) was also investigated. Arterial calcifications were detected in the posterior tibial artery in 22 (55%) beta-thalassemia patients and in six (15%) controls (P < 0.01 for the comparison). PXE skin lesions and AS were found in eight (20%) and 21 (52%) patients respectively. A total of 34 patients (85%) had at least one of the three lesions, namely, arterial calcifications, angioid streaks, and/or PXE-like skin lesions. Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid. It was concluded that arterial calcifications are common in older beta-thalassemia patients. This finding could be a manifestation of an acquired PXE syndrome associated with beta-thalassemia, and consequently, vascular events complicating PXE should be expected in these patients.

Comparative pharmacokinetics of ciprofloxacin, ofloxacin and pefloxacin in human aqueous humour.

Eighty-five patients undergoing cataract surgery were given for prophylaxis of intraocular infection two intravenous doses each of 200 mg, 300 mg or 400 mg ciprofloxacin (35 patients), 400 mg or 800 mg pefloxacin (30 patients), or 400 mg ofloxacin (20 patients). Ciprofloxacin levels in aqueous humour ranged from 0.02 to 0.50 microgram/ml, pefloxacin levels from 1.04 to 7.80 micrograms/ml, and ofloxacin levels from 0.44 to 2.27 micrograms/ml with ratios of aqueous humour to serum levels ranging from 3.8% to 25%, 21% to 48.1% and 44% to 88.4%, respectively. It is concluded that the quinolones studied might be suitable for surgical prophylaxis or treatment of anterior chamber infections due to Enterobacteriaceae, while ciprofloxacin at high doses is preferable for Pseudomonas aeruginosa infections.

Neutrophil elastase in patients with homozygous beta-thalassemia and pseudoxanthoma elasticum-like syndrome.

In this study we investigated the possible role of neutrophil (PMN) elastase and its natural inhibitor, alpha1-proteinase inhibitor (alpha1-PI) in the pathogenesis of the pseudoxanthoma elasticum (PXE)-like syndrome which is found in patients with homozygous beta-thalassemia. We studied 30 beta-thalassemia homozygotes with the PXE-like syndrome [PXE(+) group], 20 beta-thalassemia homozygotes without this syndrome [PXE(-) group] and 15 healthy controls. Plasma PMN elastase concentration in the PXE(+) and in the PXE(-) group was 136.4 +/- 89 and 163.8 +/- 126 microg/L, respectively (P > 0.05). In the control group, the concentration was 42.9 +/- 16.8 microg/L (P < 0.01 for the comparison with both patients' groups). The plasma alpha1-PI concentration in the PXE(+) and in the PXE(-) group was 2.28 +/- 0.75 and 2.6 +/- 0.96 g/L, respectively (P > 0.05). Using logistic regression, we studied the prognostic value for PXE of the following independent variables: number of transfusions, chelation therapy, mean hemoglobin concentration, PMN elastase concentration, alpha1-PI concentration, chronic transaminase elevation, and positivity for anti-HCV. None of the above variables was found to have significant prognostic value for the PXE. Plasma PMN elastase concentration is elevated in all beta-thalassemia homozygotes; its role in the pathogenesis of the PXE-like syndrome in beta-thalassemia can not be established, but our findings suggest that neutrophils of beta-thalassemia patients are activated, since PMN elastase is a marker of neutrophil activation.

Prevalence of Sjögren's-like syndrome in a cohort of HIV-1-positive patients: descriptive pathology and immunopathology.

The aims of the study were (a) to investigate the prevalence of Sjögren's-like syndrome (SLS) in an unselected population of HIV-1-positive patients and (b) to describe the pathology and immunopathology of the labial minor salivary gland biopsy. Seventy-seven HIV-1-positive patients were asked to answer the validated questionnaire of the European preliminary criteria for the classification of Sjögren's syndrome on oral and ocular sicca symptoms. Twenty-six patients gave one positive answer to both ocular and oral symptoms, and of these 14 (hepatitis C virus negative) consented to participate in the study (patients group). Ten age- and sex-matched HIV-1-positive patients with a negative questionnaire constituted the control group. Patients and controls had: (a) Schirmer's test and slit-lamp examination after Rose Bengal staining; (b) parotid gland scanning with technetium; (c) detection of autoantibodies in sera to Ro/SSA and La/SSB; (d) labial salivary gland biopsy (patients group only). The control group gave negative parotid gland scanning and only one gave a positive Rose Bengal staining test. In the patients group, parotid gland enlargement was manifested by three patients and only one gave positive Rose Bengal staining test. Six out of the 14 patients had biopsies identical with Sjögren's syndrome and five of these gave positive parotid gland scanning. In the biopsies of four other patients, mucoid degeneration of the stroma was found. Immunopathology revealed that the predominant cells were T cells with the CD8 phenotype. None of the patient and control sera had autoantibodies to Ro/SSA and La/SSB, whereas all patients had hypergammaglobulinaemia. The overall prevalence of possible SLS in a mixed population of HIV(+) patients (88.3% men and 11.7% women) was 7.79% which is >2.5 times higher than that observed in normal Greek adult females.