A randomized masked pilot clinical trial to compare the efficacy of topical 1% voriconazole ophthalmic solution as monotherapy with combination therapy of topical 0.02% polyhexamethylene biguanide and 0.02% chlorhexidine in the treatment of Acanthamoeba keratitis

PurposeTo compare the efficacy of topical voriconazole 1% and the combination therapy of 0.02% polyhexamethylene biguanide (PHMB) and 0.02% chlorhexidine for the treatment of Acanthamoeba keratitis (AK).MethodsThis is a prospective, pilot, double-masked randomized comparative study. Twenty-three eyes of 23 patients with microbiologically (smear and/or growth on culture) confirmed AK were randomized to group BG (PHMB 0.02% and chlorhexidine 0.02%) or group VZ (voriconazole 1%). Primary outcome measure was change in geometric mean (GM) of the corneal ulcer size at final visit. Secondary outcome measures were change in visual acuity.ResultsOut of 71 patients with confirmed AK seen during study period, 23 patients were recruited and 18 patients completed minimum 2 weeks of treatment and further analyzed. Ten patients received BG, whereas eight received VZ. Median ulcer size measured as GM of infiltrate decreased from 5.7 mm (IQR, 5.3–6.5 mm) (p = 0.02) to 1 mm (IQR, 0–4.3 mm) in group BG and from 4.5 mm (IQR, 1.8–5.1 mm) (p < 0.05) to 0.7 mm (IQR, 0–1.6 mm) in VZ group. Median visual acuity improved from 1.79 (IQR, 1.48–2.78) to 1.10 (IQR, 0.48–1.79) in BG group (p = 0.02) and from 1.60 (IQR, 1.00–2.78) to 0.80 (IQR, 0.48–1.30) in VZ group (p = 0.18).ConclusionThese outcomes suggest that topical VZ as a monotherapy in AK treatment is effective and comparable to BG combination therapy but needs trials with larger sample size and longer follow-up to provide conclusive evidence.Subject terms: Corneal diseases, Parasitic infection     

Morphological changes in breast tissue with menstrual cycle.

Whether the breast tissue undergoes morphologic changes in relation to the menstrual cycle had been a subject of debate. Elegant studies performed in the early 1980s provided conclusive evidence of cyclical changes in the normal breast lobules. These studies were almost entirely based on autopsy material and have not been validated in the clinical setting. In the present study, we examine breast tissues from surgical specimens from 73 premenopausal women and use morphological criteria to characterize the stage of the menstrual cycle. Patients taking oral contraceptives or hormonal therapy were excluded from this study. The following histological parameters were used to assess the menstrual stage: number of cell layers in the acini and presence and degree of vacuolation of the myoepithelial cells, stromal edema, infiltrate, mitosis, and apoptosis. The morphological stage was then correlated with the stage of the cycle, as determined by last menstrual period and the usual menstrual cycle length and in some patients with serum estrogen and progesterone levels. The morphologic stage was concordant with dates in 54 of the 73 patients (74%, P =.001). In 31 of these patients, serum levels of estradiol and progesterone at the time of surgery were available for correlation. Twenty-five (80%) of these were phase concordant by morphology and progesterone levels (P =.01), and 25 (80%), by dates and progesterone levels (P =.007). Women with a high morphologic score were seven times as likely to be in luteal phase as were women with a low score (odds ratio, 7.1; 95% confidence interval). Menstrual phase can be determined by the morphology of the normal lobules present within the surgically excised breast specimens. This will permit retrospective analysis of large archival databases to analyze the effect of timing of surgery in relation to menstrual cycle phase. It will also aid the design of epidemiological studies for breast cancer risk assessment.     

Formulation, and Evaluation of Pentoxifylline-Loaded Poly(��-caprolactone) Microspheres

Pentoxifylline-loaded poly(ε-caprolactone) microspheres were prepared by solvent evaporation technique with different drug to carrier ratio F1 (1:3), F2 (1:4), F3 (1:5) and F4 (1:6). The microspheres were characterized for particle size, scanning electron microscopy, FT-IR study, percentage yield, drug entrapment, stability studies and for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The size of microspheres was found to be ranging 59.3±6.3μm to 86.22±4.23 μm. Among the four drug to carrier ratio, F3 (1:5) showed maximum percentage yield of 83.34±2.46% and F2 (1:4) showed highest drug entrapment of 76.92±3.24% w/w. It was found that there was no interaction between drug and polymer by FT-IR study. No appreciable difference was observed in the extent of degradation of product during 60 d in the microspheres, which were stored at various temperatures. In the in vitro release study formulation F2 (1:4) showed 90.34% drug release at 15 h and found to be sustained. The release followed Higuchi kinetics indicating diffusion controlled drug release.     

Hypocalcaemia in severe meningococcal infections

AIM: To determine the incidence of hypocalcaemia in critically ill children with meningococcal disease. METHODS: In a prospective cohort study, 70 of 80 patients admitted consecutively with a clinical diagnosis of meningococcal disease to intensive care had measurements of total and ionised calcium on admission. Parathormone and calcitonin were measured in a proportion of the children. RESULTS: Total and ionised calcium concentrations were low in 70% of the children. There was a weak relation of calcium concentration to the volume of blood derived colloid which had been given, but a good relation to disease severity, where sicker children had lower calcium concentrations. Although the parathormone concentration was higher in children with lower calcium concentrations, some children had low ionised calcium concentrations, without an increase of parathormone concentration. Serum calcitonin concentration was not related to calcium concentrations. CONCLUSION: Hypocalcaemia is common in meningococcal disease.