Pulse cyclophosphamide therapy in the management of patients with macular serpiginous choroidopathy

Purpose:

To evaluate safety and efficacy of intravenous pulse cyclophosphamide (CyP) in acute macular serpiginous choroiditis (SC).

Methods:

Patients with acute macular SC with lesions threatening and/or involving fovea were enrolled. All patients received CyP (1 g/m² ) for 3 days followed by high-dose oral steroids (1.5 mg/kg) tapered over 6 months and monitored for visual acuity, response to treatment and systemic side effects.

Results:

Eight patients (seven unilateral and one bilateral) with median age of 27 years (range: 13–40 years) were recruited. Mean visual acuity at presentation was 0.71 ± 0.35 logarithm of the minimum angle of resolution while postpulse visual acuity was 0.40 ± 0.32. Final mean visual acuity at 1-year was 0.31 ± 0.23 (P ≤ 0.05). Three eyes had recurrence and 3 patients developed transient hair loss with no other adverse effect.

Conclusion:

Intravenous CyP provides rapid resolution of lesion activity and thereby helps in maintaining good functional acuity.     

Liquid chromatography tandem mass spectrometry assay for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma and its application to a bioequivalence study

A rapid, simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for simultaneous determination of venlafaxine (VEN) and its active metabolite, O-desmethylvenlafaxine (ODV) in human plasma was developed using nadolol as internal standard (IS). The analytes and IS were extracted from 200 microl aliquots of human plasma via protein precipitation using 0.43% formic acid in acetonitrile and separated on a Hypurity cyano (50 mm x 4.6 mm, 5 microm) column. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring (MRM) and positive ion mode. The precursor to product ion transitions monitored for VEN, ODV and IS were m/z 278.3-->58.1, 264.3-->58.1 and 310.4-->254.1, respectively. The total chromatographic runtime was 3 min with retention time for VEN, ODV and IS at 1.93, 1.50 and 1.29 min, respectively. The method was fully validated for its sensitivity, accuracy and precision, linearity, recovery, matrix effect, dilution integrity and stability studies. The linear dynamic range of 2.0-500 ng/ml was established for both VEN and ODV with mean correlation coefficient (r), 0.9994 and 0.9990, respectively. The intra-batch and inter-batch precision (%CV) in three validation batches across five concentration levels (LLOQ, LQC, MQC, HQC and ULOQ) was less than 12.6% for both the analytes. The accuracy determined at these levels was within -9.8 to +3.9% in terms of %bias. The method was successfully applied to a bioequivalence study of 150 mg venlafaxine extended release capsule formulation in 22 healthy Indian male subjects under fed condition.     

Patterns of uveitis at the Apex Institute for Eye Care in India: Results from a prospectively enrolled patient data base (2011–2013)

The purpose of the study was to identify the clinical and etiological profile of uveitis at the apex institute for eye care in India. This is a prospective, prevalence study. 980 consecutive patients with uveitis referred to uvea clinic, Dr. RP Centre for Ophthalmic Sciences (Ophthalmology division, All India Institute of Medical Sciences). Demographic data of each patient were noted and a thorough ocular examination including slit lamp examination and dilated fundus evaluation was carried out. OCT and fluorescein angiography were undertaken whenever indicated. Uveitis was classified based on the anatomic location of inflammation (IUSG classification). Relevant serological and radiological investigations were obtained based on systemic symptomatology, and if the uveitis was recurrent (even in the absence of systemic symptoms). The presence of a systemic disease was confirmed by obtaining an internist consultation. The main outcome measures include pattern of uveitis according to anatomical classification and the etiology. Out of 980 patients with uveitis, 413 (42.14 %) patients had anterior uveitis, 131 (13.36 %) had intermediate uveitis, 165 (16.83 %) had posterior uveitis, 91 (9.2 %) had panuveitis, 47 (4.7 %) had retinal vasculitis, 22 (2.24 %) had scleritis, 17 (1.7 %) had masquerade syndromes, 8 (0.8 %) had keratouveitis, 22 (2.24 %) had sclerokeratouveitis, 19 (1.9 %) had endophthalmitis and 45 (4.5 %) had other causes of inflammation including trauma and intraocular surgery. Out of all uveitic patients definite etiological correlation could be made out in 225 (23 %) patients; thus 77 % were categorised as idiopathic. Only 9 % of all patients were found to have uveitis with an infectious etiology. Amongst infectious causes of uveitis tuberculosis was the leading cause, accounting for sixty percent of all infectious uveitis (approximately 5 % of overall uveitis). Non-infectious uveitis etiology accounted for more than 90 % of all cases with ankylosing spondylitis being the most common followed by sarcoidosis and juvenile rheumatoid arthritis. Amongst known uveitic syndromes serpiginous like choroidopathy was the most common and was followed by acute posterior placoid pigmented epitheliopathy and Fuch’s heterochromic iridocyclitis. Infection, including tuberculosis, is an infrequent cause of uveitis in the study population. Multicentric, collaborative efforts are required to improve levels of clinical evidence and evolve consensus in establishing stringent guidelines for labelling uveitis as being of infectious etiology.     

rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers

BACKGROUND: The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4 Delta 30 was previously found to be safe and immunogenic at a dose of 10(5) plaque-forming units (pfu). METHODS: In a follow-up placebo-controlled phase 2 clinical trial, rDEN4 Delta 30 was administered as a single inoculation to 3 separate dose cohorts (10(3) pfu, 10(2) pfu, or 10(1) pfu), for further evaluation. Each dose cohort consisted of 20 vaccinees and 4 placebo recipients. Volunteers were monitored closely for adverse events, and serum was collected on study days 28 and 42 for determination of neutralizing antibody titer. RESULTS: The vaccine was well tolerated at all doses studied. The most common adverse events observed were a transient asymptomatic rash in >50% of vaccinees and a mild neutropenia in approximately 20% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic, with 95%-100% of vaccinees in each dose cohort developing a >/=4-fold increase in titers of serum neutralizing antibodies against DEN-4. CONCLUSIONS: The rDEN4 Delta 30 vaccine is safe and induced an antibody response that was broadly neutralizing against genotypically diverse DEN-4 viruses. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.     

Anterior Pelvic Organ Prolapse Repair Using Synthetic Mesh

Since the U.S. Food and Drug Administration (FDA) statement on mesh in July of 2011, there has been controversy regarding synthetic mesh repairs for vaginal prolapse. In this article, we review the biochemical basis for the use of synthetic mesh in prolapse repair as well as clinical results of anterior compartment prolapse repair with synthetic mesh. Finally, we discuss the FDA warning regarding mesh.     

What is the cause of the opthalmoplegia in this young child? What treatment is necessary?

Not all orbital fractures are associated with clinical signs of swelling, ecchymosis, and subconjunctival hemorrhage. The “white‐eyed” blowout fracture is more commonly seen in children and is associated with entrapment of the extraocular muscles. Early surgical intervention is indicated and it must have been in the differential diagnosis of the head injury patient with opthalmoplegia.     

Short-term Intensive Immunosuppression: A Randomized,Three-arm Study of Intravenous Pulse Methylprednisolone and Cyclophosphamide in Macular Serpiginous Choroiditis

Purpose: To compare the efficacy of pulse cyclophosphamide with pulse dexamethasone in acute macular serpiginous choroiditis (SC).

Methods: A total of 30 patients with macular SC were prospectively randomized into three treatment groups: group D (pulse dexamethasone); group C (pulse cyclophosphamide); and combination (pulse group DCP) administered for 3 days. Macular SC was defined as any active lesion involving/threatening macula.

Results: A total of 30 patients were enrolled, with 10 patients in each group. Lesions completely healed at median duration of 2 weeks in each group, with significant improvement in visual acuity compared with pretreatment levels (p<0.05). Pulse cyclophosphamide was most effective in faster healing of lesions compared with other groups. There was no difference in gain in visual acuity between any of the groups (p = 0.32).

Conclusions: Cyclophosphamide may be an effective treatment modality for acute macular SC, though it may not have a long-term effect on disease relapse.     

Outcomes of open transverse abdominis release for ventral hernias: a systematic review,meta-analysis and meta-regression of factors affecting them

Hernia - The primary objectives were to evaluate Surgical Site Occurrences (SSO) and Surgical Site Occurrences requiring procedural Intervention (SSOPI) after open transversus abdominis release and...