General or Spinal Anaesthetic for Vaginal Surgery in Pelvic Floor Disorders (GOSSIP): a feasibility randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: Spinal anaesthesia (SA) and general anaesthesia (GA) are widely used techniques for vaginal surgery for pelvic floor disorders with inconclusive evidence of the superiority of either. We conducted a randomised controlled trial (RCT) to assess the feasibility of a full scale RCT aiming to examine the effect of anaesthetic mode for vaginal surgery on operative, patient reported and length of hospital stay (LOHS) outcomes. METHODS: Patients undergoing vaginal surgery, recruited through a urogynaecology service in a University teaching hospital, were randomised to receive either GA or SA. Patients were followed up for 12 weeks postoperatively. Pain was measured on a visual analogue scale; nausea was assessed with a four-point verbal rating scale. Patient's subjective perception of treatment outcome, quality of life (QoL) and functional outcomes were assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ) on vaginal symptoms and the SF-36 questionnaire. RESULTS: Sixty women were randomised, 29 to GA and 31 to SA. The groups were similar in terms of age and type of vaginal surgery performed. No statistically significant differences were noted between the groups with regard to pain, nausea, quality of life (QoL), functional outcomes as well as length of stay in the postoperative recovery room, use of analgesia postoperatively and LOHS. CONCLUSION: This study has demonstrated that a full RCT is feasible and should focus on the length of hospital stay in a subgroup of patients undergoing vaginal surgery where SA may help to facilitate enhanced recovery or day surgery.

Synchronous of breast and vulvar Paget's disease: a case report.

BACKGROUND: Synchronous Paget's disease of breast and vulva is extremely rare and has only been reported in the literature in one other case. CASE: A 58-year-old postmenopausal woman was found to have crusting, bleeding, and discharge from left nipple, as well as vulvar pruritis at the same time. Biopsy of breast lesion demonstrated Paget's disease with an underlying foci of ductal carcinoma in-situ that required total mastectomy of left breast with sentinel node biopsy and breast reconstruction. For vulvar symptoms, the patient was initially diagnosed with dermatitis and topical ointment was prescribed. However, her symptoms persisted for the next several months, and she underwent vulvar biopsy that demonstrated Paget's disease. She underwent partial vulvectomy. Multiple episodes of recurrent vulvar Paget's disease were noted in the postoperative course that medical therapy with Imiquimod and a second partial vulvectomy was performed. CONCLUSION: Synchronous of breast and vulvar Paget's disease is presented. There was a delay in diagnosing vulvar Paget's disease in this experienced case. While coincidence of breast and vulvar Paget's disease is likely, ectopic mammary tissue in vulvar as well as secondary metastasis from a focal lesion of breast Paget's disease needs to be carefully evaluated whenever the patient complains of vulvar symptoms in the setting of breast Paget's disease.

Prioritisation of teaching topics in obstetrics and gynaecology: a Delphi survey of postgraduate trainees.

Topics for theoretical teaching during the obstetrics and gynaecology specialty training programme are often chosen by tutors, with little input from the trainees. However, it is important to actively involve adults in their learning process to maintain their learning ownership and motivation. The Delphi methodology is a generic social science technique used to aggregate views and opinions of experts, the community and service users. In this study, we conducted a two generational Delphi study to achieve consensus between a group of trainees in obstetrics and gynaecology, regarding what they considered important topics for inclusion in their protected teaching programme. A total of 25 trainees from one deanery, participated in this study. We were able to produce a list of 26 topics in obstetrics and 30 in gynaecology, prioritised according to their importance for inclusion in the specialty protected teaching programme, as viewed by these trainees.

Electroencephalographic evidence for retention of olfactory cues in homing coho salmon.

Differences were observed in the magnitude of the evoked electroencephalographic response to 1 percent morpholine for homing coho salmon (Oncorhynchus kisutch) exposed to morpholine as fingerlings 1 month before smolting as compared to salmon not exposed to morpholine as fingerlings. These results indicate that olfactory information has been retained for 18 months, the period between smolting and the homeward migration.

Imprinting to chemical cues: the basis for home stream selection in salmon.

Juvenile coho salmon were exposed to morpholine or phenethyl alcohol (p-alcohol) for 1 1/2 months and then released in Lake Michigan. During the spawning migration 18 months later, morpholine and p-alcohol were metered into separate streams, and the number of morpholine- and p-alcohol-exposed fish returning to each stream was determined. Seventeen other locations were also monitored. The majority of the fish exposed to morpholine were captured in the stream scented with morpholine and most fish exposed to p-alcohol were captured at the p-alcohol-treated stream. This field study demonstrates that coho salmon imprint to and utilize chemical cues for homing.

The Evolving Theory of Evolutionary Radiations.

Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology.

Effects of changes to the stable environment on the exhalation of ethane, carbon monoxide and hydrogen peroxide by horses with respiratory inflammation.

The aim of this study was to assess the effects of changes to the stable environment on exhaled markers of respiratory inflammation in six horses with clinical histories of recurrent airway obstruction. The horses were maintained for two weeks under conventional stable management (straw bedding and hay) and for two weeks on a reduced-dust regimen (paper bedding and ensiled grass), in a crossover study design. Exhaled ethane and carbon monoxide (CO) and exhaled breath condensate hydrogen peroxide (H(2)O(2)) were measured every three days under each regimen. The presence of clinical signs of airway inflammation (nasal discharge and cough) was monitored daily. The reduced-dust regimen was associated with fewer clinical signs of airway inflammation than the conventional regimen. Exhaled ethane and CO were significantly lower on the reduced-dust regimen and these markers were correlated with clinical signs of respiratory inflammation, but exhaled H(2)O(2) was not affected by the management regimen.

Transient changes in the synthesis of nitric oxide result in long-term as well as short-term changes in acetic acid-induced writhing in mice.

A single injection of nitric oxide (NO) synthase (NOS) inhibitors prevents the development of persistent hyperalgesia induced by various manipulations, suggesting that NO precipitates long-term changes in nociception. We examined the possibility that inhibition of NOS may also be sufficient to produce long-term decreases in nociceptive assays, such as writhing, that are known to be sensitive to the short-term effects of NOS inhibitors. We characterized short- and long-term effects of NOS inhibitors, N(omega)-nitro-L-arginine (L-NAME) or 7-nitro indazole (7-NI) injected intrathecally (i.t.) in mice on acetic acid-induced writhing. Doses of L-NAME that had no effect on hot plate or tail flick latencies inhibited writhing (0. 01-30 nmol) as well as spinal nNOS activity (5 and 100 nmol) when injected i.t. 60-90 min before testing. Anti-nociception was not mimicked by D-NAME but was prevented by co-administration with the NO precursor, L-arginine. Injection i.t. of 7-NI (30 min), a selective inhibitor of neuronal NOS (nNOS), inhibited NOS activity in the spinal cord and produced anti-nociception, confirming that writhing is sensitive to inhibition of nNOS. Although the acute action of both NOS inhibitors dissipated completely by 3-6 h, a delayed and prolonged inhibition of writhing was again observed 24 h after L-NAME (5-100 nmol), a time when spinal NOS activity was no longer inhibited by L-NAME (5 and 100 nmol) or 7-NI (25 nmol). This novel effect appears to be initiated by the transient inhibition of nNOS as delayed anti-nociception was mimicked by 7-NI at doses (10-100 nmol) that no longer inhibited spinal nNOS (25 nmol) at 24 h. Co-administration with L-arginine prevented the delayed (24 h) anti-nociceptive effects of L-NAME (30 nmol). L-Arginine (30 and 100 nmol) was without effect on nociception when administered alone 60 min or 24 h prior to testing. Together these data indicate that brief changes in the activity of nNOS induce both long- as well as short-term changes in nociception.

Amelioration of CR-EAE with lisofylline: effects on mRNA levels of IL-12 and IFN-gamma in the CNS.

CR-EAE is a Th1-mediated inflammatory autoimmune demyelinating disease of the CNS and serves as a model of human multiple sclerosis. Our previous studies have shown the protective effect of orally administered lisofylline in the prevention of active and passively induced acute EAE. In our present studies we have examined the efficacy and mechanism of action of lisofylline on CR-EAE. Lisofylline decreased the number and severity of paralytic attacks in mice with relapsing EAE. The reduction of clinical disease correlated with decreased levels of mRNA levels of IFN-gamma but not of mRNA levels of IL-12. These studies suggest that lisofylline may be an effective therapeutic for established Th1 mediated autoimmune disease and that it acts by blocking IL-12R signaling and not IL-12 production in vivo.

Radical radiation therapy with 5-fluorouracil infusion and mitomycin C for oesophageal squamous carcinoma.

Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Thirty-one patients are available for a minimum follow-up of one year, 26 patients for a minimum follow-up of 2 years. All 35 patients are included in the survival and local relapse-free analysis. Survival at one year is 47% and at 2 years 28%. The local relapse-free rate at both one and 2 years is 48%. There was an improvement in survival and local relapse-free rate for the single course regimen compared to the split course; 2 years survival 48% versus 12% (p = 0.24) local relapse-free rate 79% versus 27% (p = 0.07). All patients receiving radiation and chemotherapy were compared with historical controls treated by radiation alone. This matching procedure was done independent of knowledge of outcome (two controls were matched/case). Patients were matched for age, sex. TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of prostacyclin and thromboxane synthases in placenta and placental bed after pre-eclamptic pregnancies.

Prostacyclin and thromboxane are potent antagonistic regulators of vascular tone and platelet aggregation. In pre-eclampsia, the ratio of their metabolites is decreased. Little is known about the local regulation of intrauterine prostacyclin and thromboxane production in this condition. Placenta and placental bed biopsies were obtained from uncomplicated and pre-eclamptic pregnancies. Prostacyclin synthase (PCS) and thromboxane synthase (TXS) and their mRNA's were localized by immunohistochemistry using monoclonal antibodies and in situ hybridization. Protein and mRNA levels were quantified by immunoblot and RNase protection assay. PCS-like immunoreactivity was found in endothelial cells and leiomyocytes, whereas fetal and maternal macrophages showed positive staining for TXS. Their mRNA was localized to trophoblast and endothelium, and TXS mRNA could also be detected in macrophages. Quantitative analysis showed no significant difference in intrauterine protein or mRNA expression after pre-eclampsia. The prostacyclin and thromboxane production seems to be compartmentalized within the uteroplacental unit. The expression of their synthesizing enzymes might be regulated post-transcriptionally. Additional regulation of prostaglandin production could be metabolically or on the substrate level and requires further elucidation.

Pharmacology of the nicotinic acetylcholine receptor from fetal rat muscle expressed in Xenopus oocytes.

The fetal rat muscle nicotinic acetylcholine receptor was expressed in Xenopus oocytes. Using the voltage-clamp technique, the response to a range of agonists was measured, listed in order of (decreasing) activity efficacy: anatoxin > or = epibatidine > acetylcholine > DMPP (1,1-dimethyl-4-phenylpiperazinium) > > cytisine > pyrantel > nicotine > coniine > tubocurare > lobeline. The agonist responses were compared with the steric and electrostatic properties of the molecules, using molecular modelling. Single-channel current were measured in outside-out patches for acetylcholine, nicotine, cytisine, anatoxin and epibatidine. The conductance of the single channels was independent of the type of agonist. The mean open times were characteristic of the agonist applied. Tubocurare, better known for its antagonist properties, was also a partial agonist. Single-channel currents were also observed for tubocurare, and for methyllycaconitine in patches with a very high density of the muscle nicotinic acetylcholine receptor, and these were blocked by alpha-bungarotoxin. The agonist properties of physostigmine, galanthamine and their methyl derivatives were also investigated. The conductance of the channels observed in outside-out patches was similar to that obtained for the classical agonists. The single-channel currents observed for physostigmine, galanthamine and their methyl derivatives were blocked by alpha-bungarotoxin, methyllycaconitine and mecamylamine, in contrast to previously reported studies on neuronal and adult muscle nicotinic acetylcholine receptors.

Physostigmine, galanthamine and codeine act as 'noncompetitive nicotinic receptor agonists' on clonal rat pheochromocytoma cells.

The acetylcholine esterase inhibitor (-)-physostigmine has been shown to act as agonist on nicotinic acetylcholine receptors from muscle and brain, by binding to sites on the alpha-polypeptide that are distinct from those for the natural transmitter acetylcholine (Schröder et al., 1994). In the present report we show that (-)-physostigmine, galanthamine, and the morphine derivative codeine activate single-channel currents in outside-out patches excised from clonal rat pheochromocytoma (PC12) cells. Although several lines of evidence demonstrate that the three alkaloids act on the same channels as acetylcholine, the competitive nicotinic antagonist methyllycaconitine only inhibited channel activation by acetylcholine but not by (-)-physostigmine, galanthamine or codeine. In contrast, the monoclonal antibody FK1, which competitively inhibits (-)-physostigmine binding to nicotinic acetylcholine receptors, did not affect channel activation by acetylcholine but inhibited activation by (-)-physostigmine, galanthamine and codeine. The three alkaloids therefore act via binding sites distinct from those for acetylcholine, in a 'noncompetitive' fashion. The potency of (-)-physostigmine and related compounds to act as a noncompetitive agonist is unrelated to the level of acetylcholine esterase inhibition induced by these drugs. (-)-Physostigmine, galanthamine and codeine do not evoke sizable whole-cell currents, which is due to the combined effects of low open-channel probability, slow onset and slow inactivation of response. In contrast, they sensitize PC12 cell nicotinic receptors in their submaximal response to acetylcholine. While the abundance of nicotinic acetylcholine receptor isoforms expressed in PC12 cells excludes identification of specific nicotinic acetylcholine receptor subtypes that interact with noncompetitive agonists, the identical patterns of single-channel current amplitudes observed with acetylcholine and with noncompetitive agonists suggested that all PC12 cell nicotinic acetylcholine receptor subtypes that respond to acetylcholine also respond to noncompetitive agonist. The action of noncompetitive agonists therefore seems to be highly conserved between nicotinic acetylcholine receptor subtypes, in agreement with the high level of structural conservation in the sequence region harboring major elements of this site.

The significance of negative middle ear pressure.

An increasing body of experience is defining the value of the impedance bridge for the detection and diagnosis of otologic disorders. In this study the audiometric status of 1,133 ears is correlated with the tympanometric configuration and middle ear pressure. It is noted that the air-bone gap systematically increases as the middle ear pressure decreases from 0 to -400 mm Ho. Mildly negative middle ear pressure (Jerger's Type A Tympanogram) produces air-bone gaps statistically greater than at atmospheric pressure. These data demonstrate the magnitude of the adverse effect of negative middle ear pressure upon middle ear auditory function.

Otologic complaints in temporomandibular joint syndrome.

Complaints of diminished hearing or reduced speech discrimination frequently accompany temporomandibular dysfunction. There is no consensus as to the mechanism of their occurrence or the alteration of these symptoms with the treatment. We studied 12 subjects with internal derangement of the temporomandibular joint (treated surgically) and nine subjects with myofascial pain disorder (treated medically), and we found no difference between the groups in pretreatment audiometric findings or in their degree of otologic symptoms. Similarly, there were no differences in posttreatment audiometric measures and there were no significant treatment effects. Furthermore, there was no correlation between subjects' complaints of reduced hearing sensitivity or discrimination and audiometric results. The apparently significant reduction in symptoms experienced by some subjects in the absence of audiometric change suggests the operation of unmeasured factors in their response to treatment.

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats.

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15% protein plus 3% leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 0.6, LW = 23.1 1.0 g vs N = 29.4 1.3, L = 28.1 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 0.033 vs LW = 0.598 0.036, N = 0.623 0.062, L = 0.697 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.

High-frequency electrostimulation hearing after mastoidectomy.

This study was undertaken to measure the degree of high-frequency sensorineural hearing loss following mastoid surgery. Twenty-five patients undergoing mastoidectomy procedures were tested preoperatively, less than 2 days postoperatively, and at 30 days postoperatively using the Tonndorf Audimax 500 high-frequency audiometer. Electrostimulation thresholds in 1-kHz intervals, from 1 to 20 kHz, were measured, and the highest detectable frequency was determined to within 0.1 kHz. Surgical drilling time was recorded. Average drilling time was 51 minutes. A significant temporary threshold shift was observed, measurable at multiple frequencies, less than 48 hours after mastoidectomy. There was no clinically significant change in electrostimulation thresholds (measured in 1-kHz increments, from 1 to 16 kHz) preoperatively to 30 days postoperatively. A statistically significant average loss of 0.89 kHz in the highest frequency producing a measurable response was noted (p less than 0.05). Determinations of the highest measurable frequency may be the most sensitive measure of surgically-induced, high-frequency sensorineural hearing changes.

Predictive value of tympanometry in middle ear effusion.

The presence of middle ear effusion may be inferred from a tympanogram by the configuration of the pressure compliance curve. Not infrequently, however, effusion is absent at the time of surgery when strongly indicated by preoperative tympanometry. We evaluated this discrepancy by contrasting preoperative tympanograms with the findings at surgery in 462 children, aged 4 to 8 years, with clinical evidence of persistent effusion in 909 ears. Based on these results we can classify tympanograms as to high risk for effusion, intermediate, and low risk. The proportion of ears with effusion was 83%, 47%, and 34%, respectively. The proportion of ears with fluid in the high risk tympanogram group did not change appreciably over a 1- to 8-week period, ie, no trend toward spontaneous resolution occurred. The high incidence of effusion at surgery in our low risk group is far higher than expected and is presumably due to reinfection of these ears during the time between examination and operation.

Incidence of hearing decline in the elderly.

Pure-tone audiometry was done on 1475 persons on two occasions 6 years apart by the same audiologist in the same facility. The age of the subjects ranged from 58 to 88 years at the initial testing and 63 to 95 at the second. The average 6-year threshold change ranged from 1 to 8 dB at 250-6 kHz and 10-15 dB at 8 kHz. The differences in thresholds fell into two patterns, one for low frequencies (250-1 kHz) and the other for high frequencies (4-8 kHz). For the lows, thresholds worsened at an increasing rate with increasing age independent of the initial hearing level, and women's thresholds worsened more than men's. For the highs, the rate of threshold change decreased with age and with the initial threshold at rates that did not differ between genders. Using a change in PTA (0.5, 1, 2 kHz) of greater than 10 dB as a criterion, significant worsening occurred in the right ear in 8.5%, in the left ear in 13.5%, and in both ears of 4.1% of the subjects over the 6 year period. The rate of significant worsening increased with age. Although hearing loss increased with age, age alone accounted for less than 10% of the variance. Therefore, factors that co-vary with age may be responsible. The difference in phenomena between the low frequencies and the highs suggests that two different processes are occurring. Hair-cell degeneration is the most likely cause for the change in the high frequencies. Strial atrophy or other intracochlear processes may be the cause of the low frequency changes.

Health and Nutrition Examination Survey of 1971-75: Part I. Ear and race effects in hearing.

The Health and Nutrition Examination Survey of 1971-75 contains unique hearing data because its design permits generalization to noninstitutionalized civilians in the continental United States. Air-conduction thresholds and their relationships to age, ear, gender, frequency, and race were examined in unscreened 25- to 74-year-olds. Although the observed effects of age, gender, and frequency were expected, three aspects of the results were remarkable. First, there was support for previous observations that older females have poorer low-frequency hearing. Second, there was an ear effect among white males who had poorer 2 and 4 kHz mean thresholds on the left at all ages. Third, there was a pattern of poorer mean thresholds for blacks that was particularly evident in comparisons between black and white females.