Skin flap vaginal augmentation helps prevent and cure post obstetric fistula repair urine leakage: a critical anatomical analysis.

Our aim was to describe a new surgical method for prophylaxis/cure of post obstetric fistula repair leakage based on restoring vaginal elasticity with Singapore skin flap. The rationale for this operation was based on the integral theory: scarring removes elasticity required for independent function of oppositely acting urethral closure forces so they become 'tethered, forcibly opening the urethra when give the signal to close'. Skin graft restores elasticity and closure. Used prophylactically with Goh type 4 fistula (n = 45), 46% were dry against an expected 19%. In patients with successful fistula closure, still with severe leakage (n = 24), 71% were dry against an expected 26%. TWEETABLE ABSTRACT: Singapore skin flap restores elasticity and prevents and treats incontinence in patients with successful obstetric fistula repair.

The effect of hyperglycaemia on permeability and the expression of junctional complex molecules in human retinal and choroidal endothelial cells.

Diabetic retinopathy is the leading cause of preventable blindness in the working population and its prevalence continues to increase as the worldwide prevalence of diabetes grows. Diabetic choroidopathy is less well studied and occurs in the late stages of diabetic eye disease. The main cause of visual loss in diabetic eye disease is diabetic macular oedema caused by an increase in microvascular endothelial permeability. Endothelial cell permeability is influenced by multiple factors which have not been fully elucidated, particularly in human models. In addition, the gene and protein expression between retinal and choroidal endothelial cells, even in humans, has been shown to be heterogeneous. The aim of this project was to determine, in vitro, the effect of high glucose (25 mM) on human paracellular permeability in retinal and choroidal endothelial cells. The expression of selected tight junction molecules (Occludin, Claudin-5, JAM-A and JAM-C) and adheren junction (VE-Cadherin) molecules was also compared between retinal and choroidal endothelial cells and with high glucose. High glucose conditions significantly increased the permeability in both retinal and choroidal endothelial cells monolayers although the increase was higher in retinal endothelial cells. Under normal glucose culture conditions microarray analysis determined that occludin and claudin-5 gene expression was higher in retinal endothelial cells than choroidal endothelial cells, and western blotting indicated that claudin-5 protein expression was also higher in retinal endothelial cells whilst JAM-A, and C and VE-Cadherin levels were similar. In retinal endothelial cells exposed to high glucose claudin-5, occludin and JAM-A was found to be reduced, whereas the expression of VE-Cadherin and JAM-C was unchanged when evaluated with western blotting, immunofluorescence and qPCR. None of the proteins were significantly decreased by high glucose in choroidal endothelial cells. The increase in retinal endothelial cell permeability is likely caused by a decrease in selective tight junction protein expression, leading to increased paracellular permeability. This may indicate differences in junctional molecule regulation of permeability in retinal compared to choroidal endothelial cells.

Predicting women at risk for developing obstetric fistula: a fistula index? An observational study comparison of two cohorts.

OBJECTIVE: To ascertain if a predictor of obstructed labour and obstetric fistula (OF) occurrence could be devised. DESIGN: Observational study of two cohorts. SETTING: Selian Lutheran Mission Hospital, Arusha, Tanzania and Aberdeen Women's Centre, Freetown, Sierra Leone. POPULATION: All women presenting with OF caused by obstructed labour and all women having a normal vaginal delivery (NVD) at both institutions were eligible for the study. METHODS: All women with OF and those delivering normally had their height in centimetres measured and their intertuberous space measured by the number of examiner's knuckles admitted. The dimensions for OF and normal delivery were examined individually and multiplied to gain a 'fistula index'. MAIN OUTCOMES MEASURES: Dimensions and index were compared statistically between OF and NVD women using t tests. Sensitivity, specificity and predictive values from receiver operating characteristic curves were obtained for predicting OF. RESULTS: There were statistical differences between the groups with OF women being significantly shorter, having a smaller intertuberous space and lower fistula index than those undergoing NVD (each P < 0.001). Sensitivity was high for fistula index ≤ 507.5 (94.9%, 95% confidence interval 83.1-98.6%) and for intertuberous space of at least three knuckles (92.3%, 95% CI 79.7-97.3%) alone. CONCLUSIONS: A simple antenatal measurement of intertuberous space could screen those women at higher risk of needing medical intervention to prevent OF.

Variation in pollinator visitation among garden cultivars of marigold, portulaca, and bidens.

Due to declines in pollinator populations, many people are now interested in learning about which annual flowers they can plant in their garden to better support pollinators. However, reports of experimental evaluation of cultivars of annual flowers for attraction to pollinators are scarce. We sampled pollinators visiting six cultivars of marigold (Tagetes erecta and T. patula), ten cultivars of bidens (Bidens ferulifolia and B. aurea), and eight cultivars of portulaca (Portulaca oleracea and P. grandiflora) for two years to compare pollinator visitation rates among cultivars within each flower type. Pollinators collected on flowers in research plots were categorized into four groups, honey bees (Apis mellifera), common eastern bumble bees (Bombus impatiens), wild bees, and syrphids, to show the proportion of different pollinator visitors to each cultivar. Pollinator visitation rates varied significantly among cultivars of marigold, bidens, and portulaca, with some cultivars having as much as 10-fold the visitation rate of other cultivars of the same flower type. In the second year we also evaluated nectar production and nectar quality of the most and least visited cultivars of portulaca and bidens. Our results show that pollinators have a strong preference for cultivars that produce the most nectar or nectar with the highest sugar content. This research will better inform entomologists, growers, educators, and plant breeders, about which cultivars of marigold, portulaca, and bidens are visited the most by pollinators, and how to accurately determine this at the cultivar level.

Complex interactions between nicotine and resveratrol in the Drosophila melanogaster wing spot test.

Nicotine (NIC) and resveratrol (RES) are chemicals in tobacco and wine, respectively, that are widely consumed concurrently worldwide. NIC is an alkaloid known to be toxic, addictive and to produce oxidative stress, while RES is thought of as an antioxidant with putative health benefits. Oxidative stress can induce genotoxic damage, yet few studies have examined whether NIC is genotoxic in vivo. In vitro studies have shown that RES can ameliorate deleterious effects of NIC. However, RES has been reported to have both antioxidant and pro-oxidant effects, and an in vivo study reported that 0.011 mM RES was genotoxic. We used the Drosophila melanogaster wing spot test to determine whether NIC and RES, first individually and then in combination, were genotoxic and/or altered the cell division. We hypothesized that RES would modulate NIC's effects. NIC was genotoxic in the standard (ST) cross in a concentration-independent manner, but not genotoxic in the high bioactivation (HB) cross. RES was not genotoxic in either the ST or HB cross at the concentrations tested. We discovered a complex interaction between NIC and RES. Depending on concentration, RES was protective of NIC's genotoxic damage, RES had no interaction with NIC, or RES had an additive or synergistic effect, increasing NIC's genotoxic damage. Most NIC, RES, and NIC/RES combinations tested altered the cell division in the ST and HB crosses. Because we used the ST and HB crosses, we demonstrated that genotoxicity and cell division alterations were modulated by the xenobiotic metabolism. These results provide evidence of NIC's genotoxicity in vivo at specific concentrations. Moreover, NIC's genotoxicity can be modulated by its interaction with RES in a complex manner, in which their interaction can lead to either increasing NIC's damage or protecting against it.

Pregnancy following obstetric fistula repair, the management of delivery.

Obstetric fistula patients invariably have dreadful obstetric histories. The antecedent delivery usually ends in a stillbirth and even multiparous obstetric fistula patients often have previous histories of multiple stillbirths and neonatal deaths. There is very little published on subsequent pregnancies following obstetric fistula repair or even on reproductive capabilities after repair. This study examines 49 pregnancies following obstetric fistula repair and the management and outcome of delivery.

Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep.

The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.

Women with obstetric fistula in Ethiopia: a 6-month follow up after surgical treatment.

OBJECTIVE: To quantify surgical and quality of life outcomes 6 months after obstetric fistula repair. DESIGN: A prospective study. Women were examined and questioned at discharge and at follow-up appointment. SETTING: The Barhirdar Hamlin Fistula Centre, a dedicated unit treating women with obstetric fistula in northern Ethiopia. POPULATION: All women admitted to the Barhirdar Hamlin Fistula Centre suffering from vesicovaginal (WF) and rectovaginal fistulae (RVF). METHODS: All women were asked to return for a follow-up appointment 6 months after surgical treatment. A standardised questionnaire and examination were used and information entered into a database. MAIN OUTCOMES MEASURES: Urinary and anal continence status; extent of return to previous family situation, employment, social activities and reproductive capabilities. RESULTS: Continence status at discharge was largely maintained at 6 months and quality of life was improved. Many of those incontinent on discharge improved; a small number apparently cured at discharge had later recurrence of incontinence. CONCLUSIONS: Surgical treatment for obstetric fistula is successful in maintaining continence and improving quality of life of women at 6-months follow up.

The circumferential obstetric fistula: characteristics, management and outcomes.

Obstetric vesicovaginal fistula is a tragic injury that is widespread in any country where access to emergency obstetric care is limited. More and more people are now interested in treating and caring for these women, but little is known about surgical management, and most operators have developed their own methods through years of experience. One of the more challenging cases to get a functional repair is in those women who have a circumferential defect in the bladder/urethra. This article analyses a series of 77 consecutive circumferential obstetric fistula cases operated in the Barhirdar Hamlin Fistula Centre by the author.

The impact of surgical treatment on the mental health of women with obstetric fistula.

Obstetric fistula is estimated to affect 2 million women worldwide and has considerable social and psychological effects on affected individuals. In this prospective study, 51 consecutive women with obstetric fistula admitted to the Barhirdar Hamlin Fistula Centre in the north of Ethiopia were screened using the General Health Questionnaire (GHQ-28) for potential mental health disorder before and 2 weeks after fistula surgery. Prior to surgery, all women screened positive. By 2 weeks after, this had dropped to 36% (P = 0.005). 27% of the 45 women who were cured of their incontinence screened positive, while all 6 of those with severe residual incontinence continued to screen positive. We conclude that surgical treatment of obstetric fistula results in marked improvements in mental heath.

Obstetric fistula: clinical considerations in the creation of a new urethra and the management of a subsequent pregnancy.

The paper presents two case studies to illustrate the complexity of repairing obstetric fistula (OF) with neourethral construction when complete circumferential destruction occurred. Using fictitious names, the author describes the personal story and contexts leading to OF development and depression, surgical options, and the prognosis of repair. These cases were documented at the Barhirdar Hamlin Fistula Center in Northern Ethiopia.

Effect of age related macular degeneration on the Eger macular stressometer photostress recovery time.

AIM: To assess the repeatability of Eger macular stressometer (EMS) measures of photostress recovery and determine their association with other measures of visual function. METHODS: EMS photostress recovery time was measured in 90 patients with bilateral exudative age related macular degeneration (AMD), 19 with bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD 13) years). Measurements were made on two occasions separated by 1 year. Intrasession repeatability was assessed by repeating the measures after a 10 minute recovery period at the first visit. Distance visual acuity was measured with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast sensitivity with a Pelli-Robson chart, and the presence of central visual disturbance assessed with an Amsler grid. A questionnaire was used to assess self reported difficulties with glare recovery. RESULTS: The average EMS recovery time was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated measurement (p<0.05). EMS photostress recovery was not correlated with visual function measures or subjective difficulties with lights (p>0.05). EMS photostress recovery time did not predict those whose vision decreased over the following year compared with those among whom it remained stable. CONCLUSIONS: The EMS test is not a useful tool in determining the severity or progression of AMD.

Lack of value of the Martius fibrofatty graft in obstetric fistula repair.

OBJECTIVE: To ascertain if the Martius graft is of benefit to successful surgical outcome in obstetric fistula repair. METHOD: A retrospective analysis of 440 consecutive obstetric fistula repairs performed by the author in the Addis Ababa Fistula Hospital, Ethiopia or the Barhirdar Hamlin Fistula Center, Ethiopia, with or without the Martius fibrofatty graft. These were further divided into 13 subgroups of vesicovaginal fistula and all groups compared against two outcomes; fistula closure and presence of residual urethral incontinence following repair. Results were statistically analyzed with the Fisher's exact or Chi-squared test. RESULTS: There was no statistical difference between groups with regards to breakdown of repair but a higher rate of residual incontinence in 3 subgroups with the Martius graft. CONCLUSION: The Martius graft can be safely omitted from obstetric fistula repair if the surgeon is experienced, and performs the same type of repair as used in this analysis.

Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells.

AIM: To develop a method for the reliable isolation of adult human macular inner choroidal endothelial cells (ICECs) and to subsequently characterise them for their expression of a range of endothelial cell associated surface markers. METHOD: Human ICECs were isolated after manual dissection of maculas from fresh human posterior segments. Following enzyme digestion to form a single cell suspension, the ICECs were isolated using anti-CD31 coated Dynabeads. The isolated cells were grown in culture and examined for typical endothelial cell morphology, surface expression of vWf, CD 31, CD 105, VEGF receptors 1 and 2, and expression of E-selectin after stimulation with TNF-alpha. The cells were also examined for their ability to form fenestrations and capillary-like tubes in Matrigel. RESULTS: The method enabled the rapid isolation of viable cells that demonstrated typical endothelial cobblestone morphology in culture. The cells stained positive for CD31, vWf, CD105, VEGF receptors 1 and 2, and E-selectin (after stimulation with TNF-alpha). The cells stained negative for alpha smooth muscle actin and fibroblast surface protein. The cells also developed fenestrations when cultured on fibronectin coated plates and formed capillary-like tubes structures when cultured on Matrigel. CONCLUSIONS: This technique isolates cells from the human macular inner choroid that display features consistent with vascular endothelial cells. These cells could subsequently be used to further the understanding of the pathophysiological mechanisms of diseases of the inner choroid, such as choroidal neovascularisation.

The neurophysiology of taste and olfaction in primates, and umami flavor.

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas.

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

Cephalexin therapy for infections in the elderly and other vulnerable patients.

A multicentre study was carried out in general practice to investigate the efficacy, safety and tolerance of cephalexin in the treatment of infections in 194 patients with an underlying chronic disease or other complications, and in patients over the age of 65 years. For comparison, a group of 145 patients with no such complicating conditions was included in the study. Altogether, 339 patients were treated with doses of 1 g or 2 g cephalexin daily depending on the type and severity of infection. After treatment for 5 days, over 80% of patients were cured or much improved, with no differences between the two groups. Of the 95 patients who received 10-days' treatment, the clinical outcome was considered satisfactory in approximately 80% in both groups. No clinically significant biochemical changes were recorded, no drug interactions with concurrent therapy were reported, and the incidence of side-effects was low.

The effect of corneal thickness on intraocular pressure measurement in patients with corneal pathology.

BACKGROUND/AIM: To compare intraocular pressure (IOP) measurements taken by the Goldmann applanation tonometer, the Tono-Pen and the ocular blood flow pneumotonometer in eyes with varying central corneal thickness (CCT) due to penetrating keratoplasty (PK), keratoconus (KC), and Fuchs' endothelial dystrophy (FED). METHODS: IOP was measured with the Goldmann applanation tonometer, Tono-Pen XL, and OBF pneumotonometer in 127 eyes with the following corneal abnormalities. There were 56 eyes that had undergone PK, 37 eyes with KC, and 34 eyes with FED. CCT was measured using an ultrasound pachymeter after IOP determinations had been made. RESULTS: Mean IOP measurements in all three patient groups were significantly higher when measured by OBF pneumotonometer. Linear regression analysis showed that patients with FED had a significant increase in IOP with increasing CCT of 0.18 mm Hg/10 microm using the Goldmann tonometer, 0.15 mm Hg/10 microm with the Tono-Pen, and 0.26 mm Hg/10 microm with the OBF pneumotonometer. In patients with KC and after PK, linear regression analysis did not show a significant effect of CCT on IOP. A multivariate linear regression model controlling for age, sex, graft size, and patient group, showed that the effect of CCT on IOP for Tono-Pen (0.13 mm Hg/10 microm CCT) and Goldmann (0.14 mm Hg/10 microm CCT) were significantly lower than for the OBF pneumotonometer (0.26 mm Hg/10 microm CCT). CONCLUSIONS: This study found that mean IOP measurements using the OBF pneumotonometer were significantly higher than those made using the Goldmann applanation tonometer or Tono-Pen in eyes with a variety of cornel pathologies. The OBF pneumotonometer was found to be most affected by variation in CCT. For all three instruments, the relation between IOP and CCT depended on the corneal pathology and was greatest for FED.