Effect of inhaled frusemide on responses of airways to bradykinin and adenosine 5'-monophosphate in asthma.

BACKGROUND--Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma. This effect could be caused by interference with neural pathways. The effect of inhaled frusemide on bronchoconstriction induced by inhaled bradykinin, which is thought to cause bronchoconstriction via neural mechanisms, was studied and compared with the effects of adenosine 5'-monophosphate (AMP) which probably produces its airway effects by augmenting mast cell mediator release and interfering with neural pathways. METHODS--Patients first underwent AMP and bradykinin challenges. They were then studied in a randomised, placebo controlled, double blind fashion. Ten atopic asthmatic subjects, studied on four days, were pretreated with inhaled frusemide (40 mg) or placebo for 10 minutes, five minutes before challenge with increasing concentrations of nebulised AMP or bradykinin. RESULTS--On the open visit days the provocative concentrations required to reduce forced expiratory volume in one second (FEV1) by 20% from baseline (PC20) for AMP and bradykinin were 16.23 (1.42-67.16) and 2.75 (0.81-6.6) mg/ml. There was a significant correlation between baseline AMP and bradykinin PC20 values. For AMP the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 80.97 (9.97- > 400.0) and 14.86 (2.6-104.6) mg/ml respectively (95% CI 0.49 to 0.98). For bradykinin the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 13.22 (2.53- > 16.0) and 2.52 (0.45-5.61) mg/ml respectively (95% CI 0.43 to 1.01). Frusemide afforded 5.45 and 5.24 fold protection against AMP and bradykinin-induced bronchoconstriction respectively. Furthermore, there was a significant correlation between protection afforded to the airways against AMP and bradykinin. CONCLUSIONS--These data suggest that inhaled frusemide affords protection against bradykinin-induced bronchoconstriction which is comparable to that against AMP, supporting a common mechanism of action for frusemide.     

Perioperative tumor localization for laparoscopic colorectal surgery

Background: Because of the inability to palpate colonic tumors during laparoscopy, their location must be precisely identified before resection is undertaken. Method: A retrospective study was performed of 58 patients in order to be able to describe our methods of tumor localization for laparoscopic colorectal operations and to review their effectiveness. Results: In all patients, the entire colon was examined preoperatively by colonoscopy. In one patient, preoperative colonoscopic localization was inaccurate. In 31 patients, tumors were easily detectable at surgery. In five patients with the tumor in the right colon, even though the lesion was not detectable at surgery, right colectomy was performed without marking because preoperative colonoscopy reliably identified the lesion adjacent to the ileocecal valve. Twenty-two patients required some type of procedure to localize the tumor. The procedures and their problems were as follows: preoperative tattoo (five)—tattoo not visualized (one); intraoperative colonoscopy alone (six), combined with intraoperative tattoo (four) or clip (three)—poor operative exposure due to bowel distension (nine), hard to see the clip (three), dislodged clip (two), inadequate resection margin (one); intraoperative proctoscopy alone (two), combined with laparoscopic stitch (two)—no problems. In no patient was tumor present at a resection line and in no patient was the wrong segment resected. Conclusions: Reliable preoperative identification of the tumor adjacent to the ileocecal valve can permit right colectomy without marking. Lesions in the upper rectum can be approached via intraoperative proctoscopy ± suture placement. If the surgeon anticipates intraoperative localization may be difficult, lesions other than rectal or cecal ones should probably be marked by preoperative tattooing. Further studies regarding the technique of tattooing are warranted. Received: 18 July 1996/Accepted: 10 March 1997     

Do skin prick and conjunctival provocation tests predict symptom severity in seasonal allergic rhinoconjunctivitis?

BACKGROUND: In the investigation of seasonal allergic rhinoconjunctivitis (SAR), quantitative skin and conjunctival allergen challenge tests are used to measure individual allergen sensitivity. These tests are reproducible and relate well to prevalence but their relationship to symptom severity is less well established. OBJECTIVE: We wished to determine if quantitative skin prick tests (QSPT) and conjunctival provocation tests (CPTs) using a single grass pollen allergen extract are reproducible and predict symptom severity in SAR. METHODS: We retrospectively analysed data from 91 participants in a previously published randomized placebo controlled study of low dosage allergen immunotherapy who were randomized to receive placebo treatment. We examined the relationship between pre-seasonal QSPT, CPT and SAR symptoms. RESULTS: We found a high level of reproducibility when repeated measures were compared for both the QSPT (P < 0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no correlation between seasonal symptom, use of rescue medication or quality of life (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen challenge tests are strongly reproducible, although there is no correlation between these tests and seasonal symptom, use of rescue medication or QOL scores.     

Sister chromatid exchanges in Chinese hamster ovary cells exposed to high intensity pulsed ultrasound: inability to confirm previous positive results

This study was undertaken in an attempt to determine a physical mechanism of action for a recently published report of a small but statistically significant increase in sister chromatid exchanges (SCEs) in Chinese hamster ovary cells exposed to high-intensity pulsed ultrasound. The "positive" report's protocol involved a sizeable chance of ultrasound beam impingement on the side wall of the cell exposure chamber. Ten experiments per regimen were conducted; the regimens included exposures of (a) chamber center, (b) chamber wall, (c) nine grid sites, 0.5 mm between sites, and (d) nine grid sites, 1.5 mm between sites. The last was an exact replication of the conditions previously reported to induce the small SCE effect. The results did not support the postulate of an increase in SCEs with the ultrasound exposures.     

An explanation for the decrease in cell lysis in a rotating tube with increasing ultrasound intensity

Previous observations indicate that for in vitro mammalian cells insonated in rotating test tube the amount of cell lysis initially increases to some maximum and then decreases with further increase in ultrasound exposure. The results of the present investigation support the postulate that the reduction in cell lysis with increase in ultrasound intensity is related to the development of an ultrasonically induced "cloud" of bubbles in the fluid between the transducer and test tube; these bubbles mitigate against acoustic transmission thus reducing cell lysis in the insonated test tube.     

Investigation of a Streptococcus viridans pseudobacteremia epidemic at a university teaching hospital

For several months in 1986, an outbreak of Streptococcus viridans pseudobacteremia occurred at a large teaching hospital. All sources of laboratory blood culture contamination were excluded. A retrospective epidemiological study indicated that one phlebotomist, "P," collected a disproportionate number of the positive blood cultures. Further comparison of the paired blood culture results from the three months when the incidence was highest revealed a good concordance of results among all other phlebotomists (Kappa = 0.5), while P's results concurred with others less frequently than would be expected even by chance (Kappa less than 0.0). Clinical follow-up showed that P did not routinely wear gloves while drawing blood and had eczema of the hands. Skin scrapings from the hands, right index finger/fingernail grew predominantly S viridans species that were compatible with those recovered from contaminated blood cultures. This epidemic demonstrated the need for early detection of this source as a cause of nosocomial pseudobacteremia.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.