Morphological alterations of the abdominal wall after open incisional hernia repair with endoscopic anterior and open posterior component separation.

PURPOSE: Effects of component separation (CS) on abdominal wall morphology have only been investigated in smaller case series or cadavers. This study aimed to compare abdominal wall alterations following endoscopic anterior CS (EACS) or open transverse abdominis release (TAR). METHODS: Computed tomography scans were evaluated in patients who had undergone open incisional hernia repair with EACS or TAR. Abdominal wall circumference, lateral abdominal wall muscle thickness, and displacement were compared with (1) preoperative images after bilateral CS and (2) the undivided side postoperatively after unilateral CS. RESULTS: In total, 105 patients were included. Fifty-five (52%) and 15 (14%) underwent bilateral and unilateral EACS, respectively. Five (5%) and 14 (13%) underwent bilateral and unilateral TAR, respectively. Sixteen (15%) underwent unilateral EACS and contralateral TAR. The external oblique and transverse abdominis muscles were significantly laterally displaced with a mean of 2.74 cm (95% CI 2.29-3.19 cm, P < 0.001) and 0.82 cm (0.07-1.57 cm, P = 0.032) after EACS and TAR, respectively. The combined thickness of the lateral muscles was significantly decreased after EACS (mean decrease 10.5% (5.8-15.6%, P < 0.001)) and insignificantly decreased after TAR (mean decrease 2.6% (- 4.8 to 9.5%, P = 0.50)). The abdominal wall circumference was unchanged after bilateral (mean reduction 0.90 cm (- 0.77 to 2.58 cm), P = 0.29) and unilateral CS (mean increase 0.03 cm (- 1.01 to 1.08 cm), P = 0.95). CONCLUSION: Postoperative changes in the lateral abdominal wall musculature were different following EACS and open TAR. Either technique seems not to compromise the overall integrity of the lateral abdominal wall.

Visceral obesity is a predictor of surgical site occurrence and hernia recurrence after open abdominal wall reconstruction.

PURPOSE: High body mass index (BMI) increases the risk of postoperative complications and hernia recurrence after abdominal wall reconstruction (AWR). However, BMI does not provide specific information on the mass and distribution of adipose tissue. We hypothesized that visceral fat volume (VFV) was a better predictor than BMI for recurrence after AWR. METHODS: We included all patients undergoing AWR at our institution from November 2010 to December 2016. Data were collected from a prospective database and all patients were summoned for follow-up. VFV was calculated from preoperative CT. The primary and secondary outcomes were hernia recurrence and 30-day postoperative surgical site occurrences (SSO), respectively. RESULTS: We included a total of 154 patients. At follow-up, 42 (27.3%) patients had developed recurrence. The recurrence rate was significantly higher in patients with a VFV higher than the mean compared to a VFV lower than the mean, P = 0.004. After multivariable Cox-regression, VFV remained significantly predictive of recurrence (HR 1.09 per 0.5 L increase of VFV, P = 0.018). In contrary, BMI was not associated with hernia recurrence. There was no significant difference in the rate of SSO between patients with a VFV above and below the mean. A multivariable logistic regression model showed that VFV was significantly associated with development of SSO (OR 1.12 per 0.5 L increase, P = 0.009). CONCLUSION: VFV was significantly associated with recurrence and SSOs after AWR. This study suggests VFV as a risk assessment tool for patients undergoing AWR.

Comparison of image quality in chest, hip and pelvis examinations between mobile equipment in nursing homes and static indirect radiography equipment in the hospital.

INTRODUCTION: A hospital environment can be a significant burden and a health risk especially for dementia patients. Mobile x-ray equipment (ME) is used to enable imaging of these patients at home. The aim was to compare image quality (IQ) of chest, hip and pelvis images from ME to the stationary equipment (SE) used in a hospital department. METHODS: We analysed examinations of the chest (n = 20), hip (n = 64) and pelvis (n = 32). Images were equally obtained from each setting of ME and SE. All images were graded using Visual Grading Analysis (VGA) by three radiographers (hip and pelvis) and three radiologists (chest). Technical IQ assessment was done by 80 additional images of a Contrast-Detail Radiography phantom (CDRAD). RESULTS: All chest images were approved for diagnostic use, as well as the hip AP and pelvis images from SE. 'Approved proportion of ME images was for HIP antero-posterior (AP) and pelvis, 78% [95% CI: 52-94%] and 81% [95% CI: 54-96%] respectively. Hip axial had an overall low, but not significant different approval rate. Ordered logistic regression indicated higher IQ of HIP AP and pelvic images from SE. This contrasts that the CDRAD substudy indicated better IQ, expressed as IQFinv, from ME. CONCLUSION: The VGA showed higher IQ for the SE system, while the CDRAD showed higher IQ for the ME system. IMPLICATIONS FOR PRACTICE: Dementia patients can be examined at their home if the acquisition is optimised according to image quality in conjunct to radiation dose. Performing imaging out of the hospital and coordinating the patients' further treatment are new work areas for radiographers and requires excellent communication skills.

Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(ß2)2 nicotinic ACh receptors.

BACKGROUND AND PURPOSE: Strong implications in major neurological diseases make the neuronal α4ß2 nicotinic ACh receptor (nAChR) a highly interesting drug target. In this study, we present a detailed electrophysiological characterization of NS9283, a potent positive allosteric modulator acting selectively at 3α:2ß stoichiometry of α2* and α4* nAChRs. EXPERIMENTAL APPROACH: The whole-cell patch-clamp technique equipped with an ultra-fast drug application system was used to perform electrophysiological characterization of NS9283 modulatory actions on human α4ß2 nAChRs stably expressed in HEK293 cells (HEK293-hα4ß2). KEY RESULTS: NS9283 was demonstrated to increase the potency of ACh-evoked currents in HEK293-hα4ß2 cells by left-shifting the concentration-response curve ~60-fold. Interestingly, this modulation did not significantly alter maximal efficacy levels of ACh. Further, NS9283 did not affect the rate of desensitization of ACh-evoked currents, was incapable of reactivating desensitized receptors and only moderately slowed recovery from desensitization. However, NS9283 strongly decreased the rate of deactivation kinetics and also modestly decreased the rate of activation. This resulted in a left-shift of the ACh window current of (α4)3(ß2)2 nAChRs in the presence of NS9283. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that NS9283 increases responsiveness of human (α4)3(ß2)2 nAChR to ACh with no change in maximum efficacy. We propose that this potentiation is due to a significant slowing of deactivation kinetics. In summary, the mechanism of action of NS9283 bears high resemblance to that of benzodiazepines at the GABAA receptor and to our knowledge, NS9283 constitutes the first nAChR compound of this class.

Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors.

BACKGROUND AND PURPOSE: Positive allosteric modulation of α4ß2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH: Effects of NS9283 were evaluated in vitro using fluorescence-based Ca(2+) imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY RESULTS: NS9283 was shown to increase agonist-evoked response amplitude of (α4)(3) (ß2)(2) nACh receptors in electrophysiology paradigms. (α2)(3) (ß2)(2) , (α2)(3) (ß4)(2) and (α4)(3) (ß4)(2) were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3ß stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHßE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS: These results provide compelling evidence that positive allosteric modulators acting at the (α4)(3) (ß2)(2) nACh receptors can augment activity across a broad range of cognitive domains, and that α4ß2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.

Ultrasound-guided block of the axillary nerve: a volunteer study of a new method.

BACKGROUND: Interscalene brachial plexus block (IBPB) is the gold standard for perioperative pain management in shoulder surgery. However, a more distal technique would be desirable to avoid the side effects and potential serious complications of IBPB. Therefore, the aim of the present study was to develop and describe a new method to perform an ultrasound-guided specific axillary nerve block. METHODS: After initial investigations, 12 healthy volunteers were included. We performed an in-line ultrasound-guided specific axillary nerve block by injecting 8 ml local anesthetic (lidocaine 20 mg/ml) after placing the tip of a nerve stimulation needle cranial to the posterior circumflex humeral artery in the neurovascular space bordered by the teres minor muscle, the deltoid muscle, the triceps muscle and the shaft of the humerus. Needle placement was aided by simultaneous nerve stimulation. We assessed sensory (pinprick and cold stimulation) and motor (active resistive force) block of the axillary nerve before, 15, 30, 60, 90 and 120 min after performing the block and every 30 min until termination of the block. RESULTS: All 12 volunteers demonstrated sensory block of the axillary nerve and 10 volunteers demonstrated complete motor block. Even though it was difficult to directly visualize the axillary nerve, the block was easy to perform with easily recognizable ultrasonographic landmarks. Block duration was approximately 120 min. CONCLUSIONS: We describe a new ultrasound-guided technique to specifically block the axillary nerve. The potential clinical role of this new block remains to be determined.

[Ogilvie syndrome]. / Ogilvies syndrom.

Ogilvie's syndrome is a rare condition with progressive dilatation of the proximal colon without mechanical obstruction. Untreated it can lead to coecal perforation, peritonitis and death. It develops in patients with medical or surgical complications, but can be idiopathic. Caesarean section is the most common preceding surgical procedure. An imbalance between the parasympathetic and the sympathetic innervation of the intestine is thought to be the cause. Trauma to the retroperitoneum, infections, bleeding and electrolyte disturbances, hormonal changes and medicamina are predisposing factors. The syndrome can result in perforation of the coecum as early as the third or fourth day. Therefore a diagnostic abdominal X-ray should not be delayed by the intermittent presence of flatus and stool which is characteristic for this pseudo-obstructive condition. Medical treatment with neostigmine may be successful, coloscopic decompression of the colon is effective as is placing a tube in or close to coecum. If laparotomy is necessary, coecostomy has lower mortality than ileo-coecal resection.

Identification of amino acid residues in GluR1 responsible for ligand binding and desensitization.

Although GluR1(o) and GluR3(o) are homologous at the amino acid level, GluR3(o) desensitizes approximately threefold faster than GluR1(o). By creating chimeras of GluR1(o) and GluR3(o) and point amino acid exchanges in their S2 regions, two residues were identified to be critical for GluR1(o) desensitization: Y716 and the R/G RNA-edited site, R757. With creation of the double-point mutant (Y716F, R757G)GluR1(o), complete exchange of the desensitization rate of GluR1(o) to that of GluR3(o) was obtained. In addition, both the potency and affinity of the subtype-selective agonist bromohomoibotenic acid were exchanged by the Y716F mutation. A model is proposed of the AMPA receptor binding site whereby a hydrogen-bonding matrix of water molecules plays an important role in determining both ligand affinity and receptor desensitization properties. Residues Y716 in GluR1 and F728 in GluR3 differentially interact with this matrix to affect the binding affinity of some ligands, providing the possibility of developing subtype-selective compounds.

Agonist discrimination between AMPA receptor subtypes.

The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H]AMPA radioligand binding experiments. (S)-4-bromohomoibotenic acid (BrHIBO) exhibited a 126-fold selectivity for GluR1o compared to GluR3o. Xenopus laevis oocytes were used to express functional homomeric and heteromeric recombinant AMPA-R and to determine BrHIBO potency (EC50) at these channels. (R,S)-BrHIBO exhibited a 37-fold selectivity range amongst the AMPA-R. It is hoped that BrHIBO can be used as a lead structure for the development of other subtype-selective compounds.

Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus.

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.

Prolonged intrathecal chemotherapy replacing cranial irradiation in high-risk acute lymphatic leukaemia: long-term follow up with cerebral computed tomography scans and endocrinological studies.

UNLABELLED: Cranial irradiation in children with acute lymphatic leukaemia (ALL) decreases the risk of CNS relapse but is associated with serious long-term side-effects. We present the long-term outcome of 21 children with high-risk ALL who received prolonged intrathecal chemotherapy instead of the recommended cranial irradiation. Intrathecal triple therapy (methotrexate, hydrocortisone, and cytarabine) was administered every 2nd month throughout the maintenance phase. The average number of courses of intrathecal methotrexate was 8.7 and of triple 9.0. The 5-year event-free survival was 79%. No CNS relapses occurred. CT scan was performed at diagnosis, at cessation of therapy, and 3 years thereafter. No density abnormalities, pathological contrast enhancement, ventricular dilatation, or calcifications were found. One child showed cortical atrophy both at diagnosis and at cessation of therapy. There was a slight decrease in height SDS with time but no change in weight SDS. Delayed bone age was found in 5 children. No abnormalities of growth hormone, thyroid, adrenal, or gonadal function were observed. CONCLUSION: The study indicates that extended intrathecal chemotherapy in children with high-risk ALL may provide an effective protection from CNS relapses and is associated with a low risk of long-term side-effects.

[Surgical treatment of dumping by the Lygidakis' method]. / Operativ behandling af dumping ad modum Lygidakis.

Dumping is a common adverse effect of gastrectomy and severe dumping is one of the most intractable conditions in gastroenterology. When medical treatment and diet are insufficient, different operative techniques have been tried, all with an unsatisfactory rate of success. The Lygidakis technique for operative treatment of postgastrectomy-dumping is presented, and results from operations on four patients presented. The results obtained are promising, and Lygidakis operation may be considered as an important alternative to wellknown operative techniques when medical treatment or diet is without effect on severe dumping.

[Stress fractures]. / Stressfraktur.

The authors present stress fracture (fatigue fracture). Theories about the cause, the underlying mechanism, etiology, pathology, localisation, diagnoses and treatment are discussed, and two case histories are mentioned. Suitable precautions are recommended for runners. The authors would like to emphasize the importance of further investigations including technetium scintigraphic, in cases where stress fracture is suspected.

Radiographic contrast media and release of neutrophil specific proteins in vitro and after intravenous injection.

The neutrophil granulocytes contain granules in which different proteins are present. When activated the neutrophils degranulate and thereby release some of these proteins to the surroundings. Some of these proteins are specific for this type of cell, e.g., lactoferrin and elastase. To investigate the influence of contrast media (CM) on this release, blood was incubated with diatrizoate, ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at different concentrations, and the amount of the neutrophil specific proteins lactoferrin and elastase were measured. Decreasing protein concentrations were observed for increased medium concentrations, suggesting that the degranulation process of the neutrophils was inhibited by the CM. The protein concentrations were lowest after incubation with the two ionic media diatrizoate and ioxaglate. Significantly decreased values of plasma lactoferrin were observed one min after i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There was no significant difference between the two CM.

Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies.

The aim of this study was to investigate the relation between Antabus dosage and the disulfiram-alcohol reaction (DAR) after ethanol challenge. Fifty-two healthy volunteers, 29 men and 23 women, aged 20-61 years, were treated with increasing doses of Antabuse (1, 100, 200, 300 mg) for 14 days each. At the end of each 14 days the volunteers were challenged with 0.15 g ethanol/kg body weight. Blood pressure, pulse rate, respiration rate, and symptoms such as flushing, heat sensation, nausea, vomiting, palpitations, breathlessness, and headache were monitored for the next 50 min. The volunteers left the study when they had experienced a valid DAR. A valid DAR, which was principally defined on the basis of the patients' feeling of discomfort, but for safety reasons also on the basis of unacceptable circulatory changes, was reached in 21 out of 52 volunteers after 100 mg Antabuse, in 27 after 200 mg, and in 4 after 300 mg. Most of them left the study after flushing and circulatory changes, but did not feel ill enough to be convinced that they should abstain from drinking. Ten volunteers with weak subjective symptoms, but with a valid DAR, were therefore rechallenged after the next increased dose and experienced a somewhat stronger reaction. We conclude that a daily dose of 200 mg Antabuse brings about a substantial reaction in volunteers in the presence of alcohol. The possible need for a 300 mg dose of Antabuse to prevent a patient from drinking was discussed.