Predicting the risk of failure of closure of obstetric fistula and residual urinary incontinence using a classification system

The aim of this study is to assess the possibility of predicting the risk of failure of closure and post-fistula urinary incontinence. Women attending the fistula clinics were assessed pre-operatively, and fistulae were staged prospectively, using a previously published classification system. Assessment for fistula closure and residual urinary incontinence was performed, prior to discharge. Of the 987 women who were assessed, 960 had successful closure of their fistulae. Of those with successful closure, 229 complained of urinary incontinence following surgery. Women with fistulae located closest to the external urinary meatus had the highest rate of urinary incontinence following fistula closure. Women with significant vaginal scarring and circumferential fistulae also had significantly higher rates of urinary incontinence and higher risk of failure of closure. The classification used is able to predict women at risk of post-fistula urinary incontinence and failure of closure.     

Symptomatic Giant Virchow-Robin Spaces: A Rare Cause of Spastic Quadriparesis in 43-Year-old Ethiopian Patient: A Case Report

BackgroundVirchow-Robin Spaces (VRS) are perivascular spaces that surround small arteries and arterioles. These normal anatomical structures are thought to be involved in the drainage of interstitial fluid and also to play an immunomodulatory role by hosting macrophages. Rarely, it becomes giant and symptomatic resulting in mass effect on adjacent neuronal structures and ventricular system causing different neurological disorders.Case PresentationWe report a 43-year-old, Ethiopian woman who presented with progressive weakness of all her extremity over the period of seven years. She had associated speech difficulty, visual blurring and pseudo-bulbar affect. Neurologic examination revealed spastic quadriparesis with increased deep tendon reflexes and up going plantar bilaterally. She had horizontal nystagmus, dysarthria and reduced bilateral visual acuity, otherwise normal cognition and cranial nerves examination. Brain MRI showed T1 hypointense, T2 hyperintense and non-enhancing multiple cystic lesions of different size, mainly in bilateral basal ganglia area with mass effect on adjacent internal capsule and lateral ventricles. Considering her clinical presentation and typical radiological features, diagnosis of symptomatic dilated Virchow-Robin spaces was made, and the patient was treated symptomatically.ConclusionCommonly, dilation of Virchow-Robin spaces are not symptomatic, but giant Virchow-Robin spaces, as in our patient may result in spastic quadriparesis, causing great disability on the patient. Thus, we recommend considering symptomatic Virchow-Robin spaces as a potential differential diagnosis of progressive quadriparesis, as early neurosurgical intervention may reduce the neurological complications, such as spastic quadriparesis.     

Drug release kinetics of temperature sensitive liposomes measured at high-temporal resolution with a millifluidic device

Purpose: Current release assays have inadequate temporal resolution (?～?10?s) to characterise temperature sensitive liposomes (TSL) designed for intravascular triggered drug release, where release within the first few seconds is relevant for drug delivery.

Materials and methods: We developed a novel release assay based on a millifluidic device. A 500?µm capillary tube was heated by a temperature-controlled Peltier element. A TSL solution encapsulating a fluorescent compound was pumped through the tube, producing a fluorescence gradient along the tube due to TSL release. Release kinetics were measured by analysing fluorescence images of the tube. We measured three TSL formulations: traditional TSL (DPPC:DSPC:DSPE-PEF2000,80:15:5), MSPC-LTSL (DPPC:MSPC:DSPE-PEG2000,85:10:5) and MPPC-LTSL (DPPC:MMPC:PEF2000,86:10:4). TSL were loaded with either carboxyfluorescein (CF), Calcein, tetramethylrhodamine (TMR) or doxorubicin (Dox). TSL were diluted in one of the four buffers: phosphate buffered saline (PBS), 10% bovine serum albumin (BSA) solution, foetal bovine serum (FBS) or human plasma. Release was measured between 37–45?°C.

Results: The millifluidic device allowed measurement of release kinetics within the first few seconds at ～5?ms temporal resolution. Dox had the fastest release and highest release %, followed by CF, Calcein and TMR. Of the four buffers, release was fastest in human plasma, followed by FBS, BSA and PBS.

Conclusions: The millifluidic device allows measurement of TSL release at unprecedented temporal resolution, thus allowing adequate characterisation of TSL release at time scales relevant for intravascular triggered drug release. The type of buffer and encapsulated compound significantly affect release kinetics and need to be considered when designing and evaluating novel TSL-drug combinations.     

Development of a nucleic acid sequence-based amplification assay that uses gag-based molecular beacons to distinguish between human immunodeficiency virus type 1 subtype C and C' infections in Ethiopia

A gag-based molecular beacon assay utilizing real-time nucleic acid sequence-based amplification technology has been developed to differentiate between the two genetic subclusters of human immunodeficiency virus type 1 (HIV-1) subtype C (C and C') circulating in Ethiopia. Of 41 samples, 36 could be classified as C or C' by sequencing of the gag gene. All 36 isolates were correctly identified by the gag beacon test. Three isolates with genomes that were recombinant in gag were unambiguously typed as belonging to the C' subcluster. Further analysis revealed that these contained the most sequence homology with a reference subcluster C' sequence in the target region of the beacon and hence were correct for the analyzed region. For one sample, sequencing and gag molecular beacon results did not match, while another isolate could not be detected at all by the beacon assay. Overall, high levels of sensitivity and specificity were achieved for both beacons (90.5% sensitivity and 100% specificity for the C beacon and 100% sensitivity and 95.2% specificity for the C' beacon). The availability of a diagnostic test which can quickly and reliably discriminate between C and C' HIV-1 infections in Ethiopia is an important first step toward studying their respective biological characteristics. As the assay is specific to the Ethiopian HIV-1 subtype C epidemic, it will contribute to characterizing the circulating viruses in this population, thereby generating the information necessary for the development of a potential efficacious HIV-1 vaccine appropriate for the Ethiopian context.