324 research outputs found
Interactions in cation permeation through the gramicidin channel. Cs, Rb, K, Na, Li, Tl, H, and effects of anion binding
No full textAs a prototype for binding and interaction in biological Na and K channels, the single channel conductances for Li, Na, K, Rb, Cs, H, and Tl and the membrane potentials for Tl-K mixtures are characterized for gramicidin A over wider concentration rangers than previously and analyzed using an "equilibrium domain" model that assumes a central rate-determining barrier. Peculiarities in the conductance-concentration relationship for TlF, TlNO3, and TlAc suggest that anions bind to Tl-loaded channels, and the theory is extended to allow for this. For concreteness, the selectivity of cation permeation is characterized in terms of individual binding and rate constants of this model, with the conclusions that the strongest site binds Cs greater than Rb greater than K greater than Na greater than Li, while the next strongest binds Na greater than K greater than Li greater than Rb greater than Cs. However, because Schagina, Grinfeldt, and Lev's recent finding of single filing (personal communication) indicates that the channel sites in gramicidin cannot be at equilibrium with the solution, and work in progress with Hägglund and Enos (Biophys. J. 21:26a. [Abstr.]) indicates that the simplest model adequate to account for the observed concentration-dependences of flux-ratio, conductance, I--V characteristic, and permeability has three barriers and four sites, some implications of additional rate-determining barriers at the mouth of the channel are discussed. The results are summarized using phenomenological "experimental" parameters that provide a model-independent way to represent that data concisely and which can be interpreted physically in terms of any desired model
Is chronic post-herniorrhaphy pain always chronic? A literature review
No full textGabriel Sandblom Department of Clinical Science, Intervention and Technology, Karolinska Institute, Huddinge, Sweden Introduction: Chronic post-surgery pain (CPSP) has gained increased recognition as a major factor influencing health-related quality-of-life following most surgical procedures, in particular following surgery for benign conditions. The natural course of CPSP, however, is not well-known. Methods: A literature review was undertaken, searching for studies with repeated estimates of post-herniorrhaphy pain. The hypothetical halvation time was calculated from the repeat estimates. Results: Eight studies fulfilling the criteria were identified. With one exception, the extrapolated halvation times ranged from 1.3 to 9.2 years. Discussion: Even if CPSP is generally very treatment-resistant, in many cases it eventually dissipates with time. Further studies are required to evaluate the prevalence of pain beyond the first decade. Keywords: hernia, pain, chronic post-surgery pain, neuropathic pain, halvation tim
Randomised prostate cancer screening trial: 20 year follow-up
No full textObjective To assess whether screening for prostate cancer reduces prostate cancer specific mortality. Design Population based randomised controlled trial. Setting Department of Urology, Norrkoping, and the South-East Region Prostate Cancer Register. Participants All men aged 50-69 in the city of Norrkoping, Sweden, identified in 1987 in the National Population Register (n=9026). Intervention From the study population, 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. On the first two occasions screening was done by digital rectal examination only. From 1993, this was combined with prostate specific antigen testing, with 4 mu g/L as cut off. On the fourth occasion (1996), only men aged 69 or under at the time of the investigation were invited. Main outcome measures Data on tumour stage, grade, and treatment from the South East Region Prostate Cancer Register. Prostate cancer specific mortality up to 31 December 2008. Results In the four screenings from 1987 to 1996 attendance was 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), and 446/606 (74%), respectively. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13). After adjustment for age at start of the study, the hazard ratio was 1.58 (1.06 to 2.36; P=0.024). Conclusions After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group.Original Publication:Gabriel Sandblom, Eberhard Varenhorst, Johan Rosell, Owe Lofman and Per Carlsson, Randomised prostate cancer screening trial: 20 year follow-up, 2011, BRITISH MEDICAL JOURNAL, (342), d1539, .http://dx.doi.org/10.1136/bmj.d1539Copyright: Author
Ionic selectivity, saturation, and block in gramicidin a channels - II. Saturation behavior of single channel conductances and evidence for the existence of multiple binding sites in the channel
No full textA theory, recently developed by Sandblom, Eisenman and Neher (1977) for the conductance of single gramicidin A channels predicts three limiting behaviors of the relation between conductance and salt concentration. These are: (i) a saturating behavior resembling a simple adsorption isotherm at medium and high concentrations, (ii) a decrease in conductance at the highest obtainable concentrations and (iii) deviations from the isotherm at very low concentrations. Features i and ii have been described before. Experimental evidence for point iii is given here. The new feature points towards interactions among ions in the channel at ionic concentrations as low as 1–10mm.Particular emphasis is given to the behavior at very low salt concentrations and the experimental problems encountered in this situation. In addition, mutual blocking effects among monovalent ions in symmetrical salt mixtures are characterized and found to be in satisfactory agreement with theoretical expectations, based upon the single salt conductance data presented here and zero-current potentials in salt mixtures to be described in a subsequent paper
Strategies for optimisation of 177Lu-octreotate therapy – exploring local administration and combination therapy regimens
No full textNeuroendocrine tumours (NETs) are a group of heterogeneous tumour types that originate in hormone-producing organs. Patients with NETs are often diagnosed after the primary tumour has metastasised. One treatment option for these patients that has shown very promising results is systemic treatment using the radiolabelled somatostatin analogue 177Lu-octreotate. However, the outcome of this treatment is currently restricted by healthy organs at risk.
The aim of this work was to optimise 177Lu-octreotate therapy of NETs by investigating strategies based on local administration and on combination therapy regimens.
The feasibility of local treatment of liver metastases was evaluated by administering 177Lu-octreotate via isolated hepatic perfusion (IHP) in a pig animal model. During IHP, the liver was completely isolated from the systemic circulation. An intraoperative gamma detector was evaluated for the purpose of determining 177Lu activity concentration in vivo during treatment. This detector was also evaluated by assessment of its technical performance parameters using phantoms. In summary, the results showed that it could be feasible to treat patients with liver metastases from NETs with 177Luoctreotate via IHP. A relatively inhomogeneous uptake was obtained and to accurately quantify 177Lu activity concentration using an intraoperative gamma detector, measurements may need to be performed at several positions over the liver.
In the combination therapy experiments, nude mice transplanted with NETs were treated with radiation therapy alone (as 177Lu-octreotate or external beam radiotherapy) and in combination with one of the drugs gemcitabine, vandetanib, cabozantinib, or ganetespib. After treatment, tumour volume was followed and compared with that in control mice. Overall, combination treatment resulted in the largest decrease in tumour volume and the longest time to progression. The results indicated that additive, and sometimes synergistic, effects could be obtained when combining 177Luoctreotate with another drug for treatment of patients with NETs
Do postoperative complications correlate to chronic pain following inguinal hernia repair? : a prospective cohort study from the Swedish hernia register
No full textPurpose: To analyse if postoperative complications constitute a predictor for the risk of developing long-term groin pain. Methods: Population-based prospective cohort study of 30,659 patients operated for inguinal hernia 2015–2017 included in the Swedish Hernia Register. Registered post-operative complications were categorised into hematomas, surgical site infections, seromas, urinary tract complications, and acute post-operative pain. A questionnaire enquiring about groin pain was distributed to all patients 1 year after surgery. Multivariable logistic regression analysis was used to find any association between postoperative complications and reported level of pain 1 year after surgery. Results: The response rate was 64.5%. In total 19,773 eligible participants responded to the questionnaire, whereof 73.4% had undergone open anterior mesh repair and 26.6% had undergone endo-laparoscopic mesh repair. Registered postoperative complications were: 750 hematomas (2.3%), 516 surgical site infections (1.6%), 395 seromas (1.2%), 1216 urinary tract complications (3.7%), and 520 hernia repairs with acute post-operative pain (1.6%). Among patients who had undergone open anterior mesh repair, an association between persistent pain and hematomas (OR 2.03, CI 1.30–3.18), surgical site infections (OR 2.18, CI 1.27–3.73) and acute post-operative pain (OR 7.46, CI 4.02–13.87) was seen. Analysis of patients with endo-laparoscopic repair showed an association between persistent pain and acute post-operative pain (OR 9.35, CI 3.18–27.48). Conclusion: Acute postoperative pain was a strong predictor for persistent pain following both open anterior and endo-laparoscopic hernia repair. Surgical site infection and hematoma were predictors for persistent pain following open anterior hernia repair, although the rate of reported postoperative complications was low.Errata: Olsson, A., Sandblom, G., Franneby, U. et al. Correction to: Do postoperative complications correlate to chronic pain following inguinal hernia repair? A prospective cohort study from the Swedish Hernia Register. Hernia. 2023;27:481. DOI: 10.1007/s10029-023-02743-w</p
Author response to: Intraoperative gallbladder perforation and risk of postoperative abscess with or without antibiotics: national cohort study of more than 108 000 cholecystectomies
No full textSurgical Infection Society guidelines on antibiotic use in gallstone surgery: high time we crack down on prophylactic antibiotics
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