Randomised prospective single-blinded study comparing 'inside-out' versus 'outside-in' transobturator tapes in the management of urodynamic stress incontinence: 1-year outcomes from the E-TOT study.

OBJECTIVE: To compare the 'inside-out' versus 'outside-in' routes for transobturator tape insertion for urodynamic stress incontinence, and to identify independent risk factors for failure at 1 year. DESIGN: Prospective single-blinded randomised trial. SETTING: Tertiary urogynaecology centre. POPULATION: A cohort of 341 women undergoing transobturator tape procedures between April 2005 and April 2007. METHODS: Women were randomised to tension-free vaginal tape-obturator (TVT)-O for the 'inside-out' route (n = 170) and transobturator tape (TOT)-ARIS for the 'outside-in' route (n = 171). Participants completed validated symptom-severity, quality-of-life and sexual-function questionnaires before and after surgery. In addition, they completed the patient global impression of improvement questionnaire (PGI-I) and standard 1-hour pad test postoperatively. MAIN OUTCOME MEASURES: The primary outcome was the patient-reported success rate reported on the PGI-I scale. Secondary outcomes included objective cure rate and improvement in King's Health Questionnaire scores. RESULTS: A total of 341 women were recruited: 171 women to the 'outside-in' (TOT-ARIS) group and 170 to the 'inside-out' (TVT-O) group; 299 completed the 1-year follow up. The patient-reported success rate was 80% with no statistically significant differences between the groups ('outside-in' 77.6% versus 'inside-out' 81.2%; OR 1.25; 95% CI 0.71, 2.20; P = 0.54). The objective cure rate was 91% with no statistically significant difference between the groups ('outside-in' 88% versus 'inside-out' 94%; OR 2.21; 95% CI 0.85, 5.75; P = 0.157). Previous incontinence surgery (OR 1.41; 95% CI 1.18, 1.91; P = 0.029) and preoperative urgency incontinence (OR 1.78; 95% CI 1.21, 3.91, P = 0.048) were significant risk factors for failure of transobturator tape at the 1-year follow up. CONCLUSIONS: There are no significant differences in patient reported and objective cure rates between 'inside-out' and 'outside-in' transobturator tapes. Quality of life and sexual function significantly improved following surgery. Both previous incontinence surgery and preoperative urgency incontinence are associated with significantly lower patient-reported cure rates.

Montelukast in the treatment of HIV associated immune reconstitution disease.

The pathogenesis of immune reconstitution disease (IRD) is not well understood and it can be difficult to manage. Leukotrienes exert proinflammatory effects, have an important role in the innate immune response, and are relatively deficient in HIV infection. Montelukast is a leukotriene receptor antagonist (LTRA) currently licensed for the treatment of asthma. We report a series of three patients with severe HIV associated IRD (cases 1 and 2 associated with starting HAART and unresponsive to steroids), who obtained clinically dramatic responses to treatment with montelukast. The first case is of IRD to secondary syphilis and the second and third to tuberculosis. Cases 1 and 3 both relapsed after a temporary break from montelukast and resolved on restarting. Montelukast should be considered in HIV associated IRD as an alternative to steroids and where these are not effective. Leukotriene overactivity may be implicated in IRD.

Chorionicity determination in twin pregnancies: how accurate are we?

OBJECTIVES: To determine the accuracy of antenatal prediction of chorionicity in twin pregnancies in our institution. METHODS: Antenatal chorionicity was determined using the number of placental masses, the presence or absence of a twin peak sign and the fetal sex. The gestational age at assessment was documented. Postnatal diagnosis of chorionicity was determined by neonatal sex and placental pathology. RESULTS: Chorionicity was correctly determined in 95% of cases (n = 131); 91% of the monochorionic and 96% of the dichorionic pregnancies were correctly determined. If chorionicity was assessed prior to 14 weeks' gestation (n = 96) the correct diagnosis was made in all except one case. CONCLUSIONS: Ultrasound assessment of chorionicity has a high sensitivity and specificity. This is further improved if the assessment is performed prior to 14 weeks' gestation.

Tractional force generation by porcine Müller cells: stimulation by growth factors in human vitreous.

PURPOSE: To examine the levels of Müller cell contraction-stimulating activity in human vitreous, correlate these levels with clinical presentation, and identify, the causative growth factors. METHODS: Human vitreous was collected from patients undergoing pars plana vitrectomy (n = 84). Müller cells were isolated from porcine retina and maintained in tissue culture. Tractional forces generated by cells incubated on three-dimensional collagen gels were measured as changes in gel thickness. Contraction-stimulating activity in vitreous (VA) was calculated from the close-response profiles of gel contraction to vitreous protein. The contributions of individual growth factors to vitreous activity (n = 10) were assessed by inhibition with specific neutralizing antibodies. RESULTS: The mean VA of patients with retinal detachment (3.65) and proliferative vitreoretinopathy stages A, B, and C (2.06) were elevated above that of patients without retinal pathology (vitreous activity = 0.23) or retinal defects alone (0.57). Mean activities in patients with epimacular proliferation (1.22) and vitreous hemorrhage (1.40) were also significantly elevated. The percentage of this activity attributable to insulin-like growth factor 1 (IGF-1) varied from 9.2% to 84.5% with a mean of 61.3%. Similarly, the percent contribution of platelet-derived growth factor (PDGF) ranged from 6.8% to 49.0% with a mean of 26.5%. CONCLUSIONS: The vitreous of patients with retinal detachment, proliferative retinal disease, and vitreous hemorrhage contain varying amounts of growth factors that stimulate tractional force generation by Müller cells. The majority of the activity can be attributed to IGF-1 and a smaller proportion to PDGF.

Quantitative vitreous collection using a modified infusion fluid during vitrectomy.

PURPOSE: To develop a vitreous sampling method that increases yield while reducing risk of harm to the patient. METHODS: Potential negative effects of fluoresceinated BSS infusion solution on biologic activity were assessed by monitoring changes in fibroblast contraction of collagen gels in response to serum or vitreous. Paired vitreous samples were collected from ten patients before and during infusion of fluoresceinated BSS solution. The extent to which the vitreous was diluted was calculated by comparing the levels of fluorescence in the samples with that in fluoresceinated BSS. Protein concentrations and levels of contraction-stimulating activity were measured for each sample. RESULTS: Fluoresceinated BSS did not alter fibroblast morphology, rate, or extent of gel contraction. Differences in corrected protein concentrations and biologic activities of the undiluted and diluted homogenous vitreous samples were not statistically significant. CONCLUSIONS: The use of fluoresceinated BSS infusion yields larger vitreous samples from which the native biochemical characteristics can be determined. Patient safety during collection is enhanced because ocular hypotony and collapse can be avoided.

Nephrolithiasis due to primary hyperparathyroidism and enteric hyperoxaluria: a case report.

Enteric hyperoxaluria and primary hyperparathyroidism have been associated with the development of nephrolithiasis. We report a case involving a patient who had hyperparathyroidism due to a parathyroid adenoma and enteric hyperoxaluria resulting from a small bowel bypass and who had severe stone-related complications. This combination of stone-generating factors has heretofore not been reported. The pathophysiology of these entities is discussed.

Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy.

OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

The information and learning needs of the caregiving family of the adult patient with cancer.

The need for information by the caregiving family of an adult patient with cancer has been identified by research. This paper is a literature review of the information and learning needs of caregiving relatives. By meeting these needs the health care professional is able to help support the family, and therefore the patient, with the difficult adjustment to the diagnosis and through the subsequent course of the disease. The health care professional facilitates the individual caregivers' coping mechanisms and the benefits can be seen in the caregiving outcome for both the family and the patient. Information needs vary from individual to individual and are dynamic throughout the cancer experience. This paper describes the role of the nurse in this area, and encourages the nurse to act as a resource person for the caregiver by the appropriate delivery of information and by ensuring that the information given to the family by other health care professionals is understood and fulfils their needs.

RNA trans-splicing in flatworms. Analysis of trans-spliced mRNAs and genes in the human parasite, Schistosoma mansoni.

Characteristics of trans-splicing in Schistosoma mansoni were examined to explore the significance and determinants of spliced leader (SL) addition in flatworms. Only a small subset of mRNAs acquire the SL. Analysis of 30 trans-spliced mRNAs and four genes revealed no discernable patterns or common characteristics in the genes, mRNAs, or their encoded proteins that might explain the functional significance of SL addition. While the mRNA encoding the glycolytic enzyme enolase is trans-spliced, mRNAs encoding four other glycolytic enzymes are not, indicating trans-splicing is not prevalent throughout this metabolic pathway. Although the 3' end of flatworm SLs contribute an AUG to mRNAs, the SL AUG does not typically serve to provide a methionine for translation initiation of reading frames in recipient mRNAs. SL RNA expression exhibits no apparent sex, tissue, or cell specificity. Trans-spliced genes undergo both cis- and trans-splicing, and the sequence contexts for these respective acceptor sites are very similar. These results suggest trans-splicing in flatworms is most likely associated either with some property conferred on recipient mRNAs by SL addition or related to some characteristic of the primary transcripts or transcription of trans-spliced genes.

Are adult children of alcoholics unique? A study of object relations and reality testing.

This self-report questionnaire study revealed that adult children of alcoholics (ACAs, n = 49) were significantly different from adult children from normal families (ACNs, (n = 55) on five of nine Bell Object Relations Reality Testing Inventory (BORRTI; Bell, 1988) scales and from adult children from dysfunctional families (ACDs, n = 48) on the Reality Testing summary score. Both ACAs and ACDs were similar to each other and different from ACNs on Insecure Attachment and on two family background ratings- perceived quality of paternal and maternal caregiving. Discussion of these results plus separate exploratory regression analyses followed.

RNA trans-splicing in Fasciola hepatica. Identification of a spliced leader (SL) RNA and SL sequences on mRNAs.

We have identified a new spliced leader (SL) in Fasciola hepatica by characterizing the 5'-terminal sequences of its enolase mRNA, an mRNA also trans-spliced in the flatworm Schistosoma mansoni (Rajkovic, A., Davis, R.E., Simonsen, J.N., and Rottman, F.M. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 8879-8883). This 37-nucleotide spliced leader is at the 5' ends of multiple Fasciola mRNAs and is likely to be derived from the 5' terminus of a nonpolyadenylated, 108-nucleotide RNA with a trimethylguanosine cap. The SL RNA gene is present in approximately 100 copies within a 1.1-kilobase genomic tandem repeat. Secondary structure predictions indicate that the Fasciola SL RNA contains three stem loops in contrast to two previously observed in S. mansoni. Fasciola and S. mansoni SLs are likely to be evolutionarily related although their sequence identity is only 65%. In contrast with nematodes, absolute conservation of SL sequences and secondary structure does not occur in trematodes. A spliced leader in Fasciola indicates that trans-splicing is likely to be a common feature in other trematodes and perhaps other flatworms.

Extracellular matrix contraction by choroidal fibroblasts: inhibition by staurosporine.

PURPOSE: To examine the potential of a broad-spectrum kinase inhibitor as a means of neutralizing the effects of contraction promoters on ocular cells. METHODS: The inhibitory effects of a broad-spectrum kinase inhibitor were examined and characterized using an in vitro assay of extracellular matrix contraction by choroidal fibroblasts. RESULTS: Staurosporine effectively inhibited collagen matrix contraction by choroidal fibroblasts. The inhibitory effects of staurosporine were rapid in onset and reversible upon removal of the inhibitor. Inhibition was observed when fibroblasts were stimulated with serum, transforming growth factor beta 1, transforming growth factor beta 2, platelet-derived growth factor, and endothelin-1. We also observed that platelet-derived growth factor and endothelin-1 stimulated only modest amounts of matrix contraction compared to transforming growth factor beta. CONCLUSIONS: Matrix contraction by cells, as observed in the development of tractional forces, can be modulated by a broad-spectrum kinase inhibitor. The marginal contractile responses of choroidal fibroblasts to platelet-derived growth factor and endothelin-1, both potent promoters of dermal fibroblast contraction, suggest that there are substantive difference in the responses of these two cell types to growth factors.

Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility.

A cDNA encoding a unique hyaluronan receptor has been molecularly cloned from a lambda GT11 3T3 cDNA expression library. Immunoblot analyses of cell lysates, using antibodies to peptides encoded in the cDNA, specifically react with a 58-kD protein. This protein is regulated by the mutant H-ras gene in cells containing a metallothionein promoter H-ras hybrid gene. Further, antibodies to peptide sequences encoded in the cDNA block the increase in locomotion resulting from induction of the mutant H-ras gene in this cell line. In a transblot assay, the bacterially expressed protein binds to biotinylated hyaluronan. Antibodies to peptides encoded in the cDNA react in immunoblot assays with the 58- and 52-kD proteins of a novel hyaluronan receptor complex previously implicated in cell locomotion. Furthermore, antibodies specific to the 58- and 52-kD proteins, which block ras-induced locomotion, also cross-react with the expressed, encoded protein. The gene product described here appears to be a new type of hyaluronan receptor that is involved in cell locomotion. It is named RHAMM, an acronym for receptor for hyaluronan-mediated motility.

Eyelid conditioning and intellectual level: effects of contextual change on extinction.

A repeated acquisition-extinction paradigm was used to investigate effects of auditory-verbal cues on the ordinarily slow extinction rate of conditioned eyelid responses of mentally retarded adults. Abrupt extinction occurred as a consequence of nearly filling extinction intertrial intervals with either relevant or irrelevant phrases, but the extinction rate was unaffected by a brief phrase in place of the absent unconditioned stimulus. Also, no evidence of transfer was found following reacquisition, when verbal cues were omitted entirely from reextinction. A contextual-change hypothesis, in terms of interference with memory of the unconditioned stimulus, was suggested to account for the data.