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S Willis

Publications and source records attributed to S Willis.

At least 55 records · Page 3Linked to original sources

Exploring biomolecular recognition using optical biosensors.

Understanding the basic forces that determine molecular recognition helps to elucidate mechanisms of biological processes and facilitates discovery of innovative biotechnological methods and materials for therapeutics, diagnostics, and separation science. The ability to measure interaction properties of biological macromolecules quantitatively across a wide range of affinity, size, and purity is a growing need of studies aimed at characterizing biomolecular interactions and the structural elements that drive them. Optical biosensors have provided an increasingly impactful technology for such biomolecular interaction analyses. These biosensors record the binding and dissociation of macromolecules in real time by transducing the accumulation of mass of an analyte molecule at the sensor surface coated with ligand molecule into an optical signal. Interactions of analytes and ligands can be analyzed at a microscale and without the need to label either interactant. Sensors enable the detection of bimolecular interaction as well as multimolecular assembly. Most notably, the method is quantitative and kinetic, enabling determination of both steady-state and dynamic parameters of interaction. This article describes the basic methodology of optical biosensors and presents several examples of its use to investigate such biomolecular systems as cytokine growth factor-receptor recognition, coagulation factor assembly, and virus-cell docking.

Artifacts↗

[Colonic pouch].

The tendency towards sphincter-preserving resection for distal rectal cancers has led to a revival of the technique of coloanal anastomosis (CAA) in recent years. In order to improve functional results, creation of a colonic J-pouch in conjunction with a coloanal anastomosis (CPA) was proposed. Two different operation techniques exist: i) Double-stapling with the anastomosis close to the dentate line and ii) intersphincteric resection with the anastomosis located immediately at the dentate line. A long rectal remnant after double-stapling leads to urgency in 15% of the patients due to stool retention in the atonic remnant. No propulsive motility patterns were recorded from the pouch which is emptied passively by upper colonic peristalsis. Therefore colonic pouches should be fashioned of descending colon and should not exceed a length of 6 cm in order to prevent stool fragmentation. Under these conditions the average stool frequency is reduced from 2-6/d after CAA to 1-3/d after CPA. This effect is maximal during the first postoperative months, but is still significant after 3 years. Colonic pouch construction also leads, due to better blood supply and prevention of pelvic hematomas, to a significant decrease of the anastomotic insufficiency rate from 10.0% after CAA to 5.4% after CPA. Therefore creation of a colonic J-pouch should be combined with coloanal reconstruction if the oncologic situation allows a sphincter-preserving procedure.

Anastomosis, Surgical↗

Experimental studies on small intestinal pouch motility and evacuation.

UNLABELLED: The aim of the study was to investigate pouch motility and evacuation under standardised conditions with a minimum of external influence. METHODS: Ileal J-pouches had been constructed 30 cm proximal to the ileocecal valve in 10 dogs (6 pelvic/4 gastric configuration). After 8 weeks the following examinations were performed: (1) measurement of pouch compliance by balloon distension, (2) measurement of pouch contractions by strain gauge transducers, (3) radiological imaging of pouch contractions and evacuation, (4) evacuation scintigraphy and (5) radiological determination of small intestinal transit time. RESULTS: Compliance (2.3 +/- 1.1 mmHg/ml) and small intestinal transit time (31.6 +/- 7.5 h) were significantly higher in the pouch group than in controls (0.5 +/- 0.2 mmHg/ml, 8.0 +/- 2.8 h; p < 0.05). Scintigraphy and radiography showed delayed pouch evacuation (t(1/2) = 109 +/- 52 min). Strain gauge measurements revealed irregular pouch contractions without detectable propagation. Contraction amplitudes (40.4 +/- 22.9 g) and frequencies (10.4 +/- 1.0/min) were equal all over the pouch. There were no functional differences between gastric and pelvic pouch configuration. CONCLUSION: Small intestinal pouches act as reservoirs. Uncoordinated motility patterns contribute to this function. Other factors than pouch motility are responsible for evacuation.

Animals↗

[Ulcerative colitis--late functional results of ileoanal pouch anastomosis].

Stool frequency after ileal pouch-anal anastomosis (IPAA) is about 5/day after adaptation during the first year. It depends on stool volume and pouch capacity, not on the design of the pouch. In most cases evacuation is spontaneous and as complete as in healthy rectum. 67% of patients are perfectly continent, while 19% have to wear pads due to intermittent leakage. Complete incontinence is reported in 0-4% of the patients. Preservation of the anal transitional zone by the double-stapling technique does not improve functional results when compared to endoanal mucosectomy or intersphincteric resection. Impairment of continence is caused by damage of the internal sphincter with consecutive decrease of the pouch-anal pressure gradient. Despite altered reflex activity, stool discrimination is preserved in most patients. The loss of colonic water and electrolyte absorption is compensated by decreased renal excretion. Alterations in bile acid metabolism are lower after IPAA than after ileostomy. Bacterial overgrowth may lead to deterioration of the functional results.

Anastomosis, Surgical↗

Foundations for a healthy future.

Health promotion activities with children and young people are important as they take messages about health seriously and can be influential in spreading messages about healthy living to their friends and families. Child health professionals have an important role to play in passing on messages of positive health to children and young people. Peer education is a useful way of passing on messages about health to young people. This article shares examples of three health promotion projects with children in a community trust, looking at asthma, sex education and testicular examination.

Adolescent↗

Is the phonological loop responsible for intelligence-related differences in forward digit span?

Children with mild mental retardation were compared with CA-matched and verbal-age-matched children without mental retardation on a forward digit span task. Forward digit span is typically used as a measure of the phonological loop (Baddeley, 1986). We hypothesized that intelligence-related differences in forward digit span are largely due to central executive functioning rather than phonological loop functioning. Results showed that the highly significant group difference in forward digit span was reduced to nonsignificance when a measure of central executive functioning was covaried out.

Attention↗

[Direct ileum pouch-anal anastomosis in ulcerative colitis: function and complications after stapler technique].

Stapled ileal pouch-anal anastomosis after proctocolectomy enables a continence preserving reconstruction. We assessed complications and functional outcome after ileoanal pouch-anastomosis in 86 consecutive patients with ulcerative colitis. There was no postoperative mortality. 2 patients required permanent ileostomy and pouch excision for manifestation of unsuspected Crohn's disease. Major postoperative complications consisted of pelvic sepsis (n = 2), anastomotic leakage (n = 4), bleeding (n = 1), pancreatitis (n = 3) and peritonitis (n = 1). Both frequencies of bowel movements and degree of continence improved with time. Two years after take down of the deviation ileostomy frequency of bowel movements was 5,6 [2]/die. At this time no patient complained of major incontinence. Minor incontinence was reported with 9% and 14% during day-time and night-time respectively. It is concluded that direct stapled ileal pouch-anal anastomosis is a safe procedure with excellent functional results for patients with ulcerative colitis.

Adolescent↗

[Value of intraluminal intestinal decompression by endoscopic placement of a Dennis tube in therapy of ileus. Retrospective clinical study of 174 patients].

For determination of the efficacy of intraluminal bowel decompression by an endoscopically placed Dennis tube, 174 patients with paralytic ileus or different kinds of partial small bowel obstruction were reviewed retrospectively. There were 66 cases (37.9%) of early postoperative ileus (A), 27 (15.5%) of late postoperative ileus (B), 38 (21.8%) of paralytic ileus (C), 31 (17.8%) with obstruction due to advanced intraabdominal tumors (D), and 12 (6.8%) of obstructive ileus caused by inflammatory stenosis of the small bowel in Crohn's disease (E). Successful endoscopic placement of the intestinal tube was achieved in 97.2% of patients. Placement of the tube was impossible in 5 cases. A total of 95 patients (54.6%) were successfully managed by long intestinal tube decompression. Success rates for the individual groups were 71.2% (A), 18.5% (B), 86.8% (C), 16.1% (D), and 41.7% (E). Some 75 patients (43.1%) had to be operated on because of insufficient conservative therapy. Four patients with advanced intraabdominal tumors died during the treatment with the intestinal tube; 13 patients died postoperatively. There was no tube-related mortality, but tube-related complications occurred in 6.9%. We conclude that intraluminal intestinal tube decompression after endoscopic placement provides a therapeutic tool with a concomitant low complication and high success rate in paralytic and early postoperative ileus.

Adolescent↗

[Streptococcal toxic shock-like syndrome" as a rare surgical disease picture].

In recent years there has been an increasing incidence of streptococcal toxic shock-like syndrome (TSLS) in otherwise healthy adults. It is characterized by fever, rash, hypotension and early shock with consecutive organ failure and a mortality rate of about 30%. This paper describes the history of two patients with severe streptococcal TSLS. Various aspects of the pathophysiology, diagnosis and therapy are discussed. Only early, aggressive and repeated surgical debridement can reduce the bacterial load and decrease circulating exotoxins and thereby, in combination with antibiotic therapy, decrease the high mortality of this entity.

Adult↗

[Endosonography control of percutaneous paracoccygeal drainage of deep pelvic abscesses after rectum resection].

Pelvic abscesses are severe complications after rectal surgery. In recent years, surgical drainage has been edged out by percutaneous drainage techniques. We report our experience with the drainage of postoperative pelvic abscesses via the paracoccygeal route controlled by endosonography. In eight patients the diagnosis of a retrorectal pelvic abscess was established by endosonography and confirmed by endosonographically controlled exploratory puncture. Drainage of the abscesses was performed via the paracoccygeal access route by trocar or Seldinger technique under permanent visual control by endoluminal sonography. Irrigation of the abscess cavity was than performed daily. In all cases drainage was successful without complications. Duration of drainage was 9-14 days with a mean of 10.8 days. In one patient there was a recurrence of the abscess because of early removal of the drainage catheter. Because of its overall availability and its good results, paracoccygeal percutaneous endosonographically controlled drainage seems to be a suitable uncomplicated method for drainage of postoperative pelvic abscesses.

Abdominal Abscess↗

Endoscopic therapy of benign anastomotic strictures of the colorectum by electroincision and balloon dilatation.

BACKGROUND AND STUDY AIMS: Endoscopic dilatation is the standard therapy for postoperative colorectal anastomotic strictures, although it carries the risk of perforation at the weakest part of the anastomosis. In order to minimize this risk we have developed a combined technique of endoscopic electroincision and hydraulic balloon dilatation. PATIENTS AND METHODS: Thirty-six symptomatic patients with benign colorectal anastomotic strictures were referred for endoscopic electroincision with consecutive balloon dilatation, if the diameter of the anastomosis was less than 12 mm (n = 15) or if the diameter was less than 20 mm and the patient complained of repeated obstructive symptoms under conservative therapy (n = 21). Under direct endoscopic control the scar tissue at the anastomotic line was incised radially with the tip of the polypectomy snare or with a papillotome. Endoscopic hydraulic balloon dilatation was then performed, using a pressure of 35 PSI for three minutes. An endoscopic or radiological control was carried out on the second day, and balloon dilatation was repeated if necessary. RESULTS: The combined technique of electroincision and consecutive balloon dilatation was performed successfully in 35 patients. In only one patient this therapy could not be performed, because of a long stenotic segment, and surgery was necessary. In 24 patients one single dilatation was sufficient after electroincision, whereas six patients required two, and five patients required three consecutive balloon dilatations. There were no severe complications such as bleeding or perforation. Complete follow-up evaluation was possible in 25 patients. In five cases recurrences appeared within the first year; all could be treated successfully by further balloon dilatation. CONCLUSIONS: The combination of endoscopic electroincision and hydraulic balloon dilatation leads to a high long-term clinical success with a minimum of complications. Therefore, in our opinion it is a useful method in the treatment of benign colorectal anastomotic strictures.

Anastomosis, Surgical↗

Differences in intracellular CA2+ stores of submandibular cells of adult and newborn rats.

The intracellular Ca2+ stores of submandibular acinar cells of adult and newborn rats were compared by measuring changes in cytosolic Ca2+ ([Ca2+]i) with the Ca2+-sensitive fluorescent probe, fura-2, in intact cells and 45Ca2+ release in permeabilized cells. In cells of adult rats, acetylcholine (ACh) and thapsigargin (TG) elicited, respectively, a 105% and 125% net increase in [Ca2+]i in Ca2+-free medium. In cells of newborn animals, the ACh-induced [Ca2+]i increase (218%) was larger; but the TG-induced increase was significantly smaller (77%), suggesting that the TG-sensitive Ca2+ pump of the store is less developed, abundant, or responsive in these cells. After ACh or TG, ionomycin elicited a further Ca2+ release. Ionomycin by itself completely discharged the ACh- and TG-sensitive store in cells of mature glands but not in cells of immature glands, suggesting a further difference in the distribution of the agonist and ionomycin sensitivities in the two types of cells. After exposure to ACh + ionomycin or TG + ionomycin, collapsing the intracellular pH gradient with monensin caused a third and large Ca2+ release (262% and 289%, respectively) in cells of adult rats, but a significantly smaller release (96%, P < 0.001, and 57%, P < 0.001, respectively) in cells of newborn rats, suggesting that a third, IP3-insensitive acidic store is significantly smaller in cells of immature glands. In permeabilized and 45Ca2+-loaded cells, inositol-1,4,5-trisphosphate (IP3, 5 microM) induced an identical 45Ca2+ release (34% and 33%, respectively) in both types of cells, but TG induced a significant smaller 45Ca2+ release in cells of immature glands (15%) than in cells of mature glands (33%). Monensin discharged <10% of loaded 45Ca2+ in both types of cells, indicating that the radiotracer was not loaded into the monensin-sensitive store. These results suggest that in cells of immature glands: (1) the TG-sensitive Ca2+ pump of the IP3-sensitive store is not well developed; (ii) the IP3-sensitive store is not completely discharged by ionomycin; and (iii) an acidic store likely to be associated with secretory granules is also underdeveloped and of a smaller size than in cells of mature glands.

Acetylcholine↗

[Preoperative diagnosis of laparoscopic cholecystectomy. Is there an indication for routine intravenous cholangiography?].

In a retrospective study including 163 patients we investigated the necessity of i.v. cholangiography in preoperative routine diagnostic workup prior to laparoscopic cholecystectomy. We evaluated the evidence of i.v. cholangiography concerning the anatomy of the biliary system, the evidence of common bile duct or cystic duct stones and the influence on the further therapeutic procedure. While the common bile duct could be demonstrated in 96.3%, the cystic duct could be visualized in only 54.6%. One out of two patients with a short cystic duct was identified. Stones in the gallbladder were recognized in 72.4% of cases, while only two out of three patients with common bile duct stones were diagnosed. In nine cases a deep junction of the cystic duct was found, but there was no influence on further operative procedure. Thus we found no improvement after routine use of i.v. cholangiography concerning the evidence of common bile duct stones or avoidance of intraoperative lesions of the common bile duct. The routine use of i.v. cholangiography prior to laparoscopic cholecystectomy is therefore not justified.

Adolescent↗

[Preoperative staging of stomach carcinoma with endosonography--fact or fancy?].

From January 1993 till December 1995, a total of 116 consecutive patients with gastric carcinoma were evaluated with endosonography and the results were compared with the histology of the resected specimen. The accuracy rate of the endosonography was 80% for T1 tumors an 83% for T4 tumors, and the sensitivity and specificity in the detection of regional involved lymph nodes were 91% and 84% respectively. Therefore endosonographic staging alone ist not a valuable pretherapeutic procedure to decide about endoscopic therapy in limited and neoadjuvant chemotherapy in extended gastric carcinoma.

Adult↗

[Streptococcal toxic shock-like syndrome"--a rare complication of pyogenic skin infections].

In recent years there is an increasing incidence of streptococcal toxic shock-like syndrome in otherwise healthy adults. It is characterized by feaver, rash, hypotension and early shock with consecutive organ failure and a mortality rate of about 30%. Only early, aggressive and repeated surgical debridement can reduce the bacterial load and decrease circulating exotoxins and thereby in combination with antibiotic therapy decrease the high mortality of this entity.

Adult↗

Evidence for a Ca2+ pool associated with secretory granules in rat submandibular acinar cells.

Intracellular Ca2+ stores in rat submandibular acinar cells were characterized using the Ca(2+)-sensitive fluorescent indicator fura 2 and the radiotracer 45Ca2+. Acetylcholine induced a rapid Ca2+ release from a store sensitive to inositol 1,4,5-trisphosphate (IP3) and to thapsigargin (TG). After this store was presumably depleted, ionomycin caused a further increase in cytosolic free Ca2+ concentration ([Ca2+]i), suggesting the presence of an IP3-insensitive Ca2+ release from a store that is more extensive and heterogeneous than the IP3-sensitive one and includes a small mitochondrial component. After both of these stores had been discharged, exposure to monensin caused an additional release of Ca2+ from a third store. This store appears to be associated with secretory granules, since Ca2+ release was significantly reduced when degranulation was induced by isoprenaline. This third store appears to be insensitive to IP3, discharges Ca2+ when the pH gradient across the limiting membrane is collapsed with monensin and only in the presence of both ionomycin and monensin. Ca2+ release from this store is not by Na+/Ca2+ exchange, since simply altering [Na+]i did not cause significant Ca2+ release. In permeabilized cells, IP3 and TG released approx. 35% of 45Ca2+, and ionomycin released an additional 57%, whereas monensin only caused a small additional release, suggesting that only IP3- and ionomycin-sensitive stores are loaded with 45Ca2+ under these conditions. The absence of significant isotope uptake into the ionomycin+monensin-sensitive store may result from a low rate of tracer accumulation or from the lack of Ca2+ pumps in the store. The pattern of response was similar in the presence and absence of mitochondrial inhibitors, indicating that the store is not located in mitochondria. In summary, these results suggest that a substantial IP3-insensitive Ca2+ store is present in secretory granules in rat submandibular acinar cells.

Acetylcholine↗

Influence of the L-arginine-nitric oxide pathway on vasoactive intestinal polypeptide release and motility in the rat stomach in vitro.

Endogenous nitric oxide (NO) plays an important role as non-adrenergic, non-cholinergic inhibitory transmitter in the gastrointestinal tract, especially in sphincter regions. The aim of this study was to investigate the influence of NO on pyloric motility and on the release of vasoactive intestinal polypeptide (VIP) in the isolated perfused rat stomach in vitro. Therefore, pyloric motility was continuously recorded by a special sleeve manometry catheter placed in the pyloric region and the concentration of VIP was determined in the venous effluent of the portal vein. Arterial perfusion with the nitrate agonist sodiumnitroprusside led to a dose-dependent reduction of the pyloric motility index (basal 166 +/- 48 mm Hg/min: sodiumnitroprusside 10(-6) M 30 +/- 20 mmHg/min: sodiumnitroprusside 10(-4) M 0: n = 8. P < 0.001) while VIP release was not influenced significantly. Inhibition of endogenous NO production by the NO-synthase inhibitor NG-nitro-L-Arg (L-NNA) significantly increased pyloric motility (basal motility index 175 +/- 28 mmHg/min: L-NNA 10(-4) M 348 +/- 48 mmHg/min: n = 8, P < 0.05). This effect was completely blocked by addition of L-Arg 10(-3) M (125 +/- 45 mm Hg/min: n = 8, P < 0.01), L-NNA and L-Arg both did not influence VIP release. Stimulation of the vagal nerve (VS: 20 V, 20 Hz, 1 ms) led to a significant decrease of the pyloric motility index (basal 181 +/- 15 mmHg/min; n = 7, P < 0.05), which was consistent even after addition of L-NNA 10(-4) M (basal 338 +/- 58 mmHg/min; VS 228 +/- 30 mmHg/min; n = 7, P < 0.05). Vagal stimulation increased VIP release significantly (basal 14.9 +/- 1.4 pmol/l; VS 20.1 +/- 2.6 pmol/l; n = 7, P < 0.05) while L-NNA had no influence on vagally induced VIP release. From these data, we conclude that the pylorus of the rat is under a tonic inhibition by endogenously released NO. Under the conditions studied. NO seems not to mediate the inhibitory effect of vagal stimulation exclusively and there seems to be no interaction between NO and VIP in the rat pylorus.

Animals↗

Evidence for reduced capacity for Ca2+ removal from the cytosol in submandibular cells of newborn rats.

The increase in cytosolic free Ca2+ concentration ([Ca2+]i) seen in submandibular cells of early postnatal rats following exposure to acetylcholine (ACh) is larger than in cells of adult rats. To elucidate possible reasons for this difference, we compared Ca2+ movements through Ca2+ pumps in both types of cells using Ca(2+)-sensitive fluorescent probe fura-2 and the radiotracer 45Ca2+. Ca2+ release induced by endoplasmic reticulum (ER) Ca(2+)-pump inhibitor thapsigargin (TG) was significantly smaller in neonatal cells than in adult cells, whereas the inositol 1,4,5-trisphosphate (IP3)-elicited Ca2+ release was comparable in both cell types. This suggests that although the size of the IP3-sensitive Ca2+ pool is adequate in immature cells, the activity of TG-sensitive Ca2+ pump in this pool is lower. The activity of the plasma membrane (PM) Ca(2+)-pump, measured by extrusion of 45Ca2+, was also significantly lower in immature cells. These results indicate that both ER and PM Ca2+ pumps may be functionally underdeveloped in immature cells, and that the enhanced increase of [Ca2+]i seen in response to ACh in immature cells may be partially, if not completely, due to a reduced capacity for removal of Ca2+ from the cytosol by active mechanisms.

Acetylcholine↗