The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Robotic telesurgery for achalasia

The craft of surgery has always relied on the use of instruments. Innovations in surgery have paralleled innovations in instrumentation. Advances in surgical instrumentation continue today and have enabled huge strides in surgical procedures and outcomes during this generation. Computers and related technology are now changing the interface between the surgeon and the patient, and are poised to improve patient outcomes by enhancing the surgeon’s skills and training. The application of computer enhanced telemanipulators, or “robots”, may specifically enhance operations, for example Heller myotomy, that require good visualization and precise careful dissection of delicate structures. This review covers the pathophysiology of achalasia and its history of medical and surgical treatment, leading to modern robotic telesurgical approaches. Improvements in outcome from medical to standard surgical to robotic telesurgical approaches are discussed. Current operative technique for robotic telesurgical treatment of achalasia is described and the authors conclude with a glimpse of where, in the future, current research endeavors will lead us in the treatment of achalasia.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score.

Burning mouth syndrome (BMS) is often an idiopathic chronic and intractable pain condition, affecting 1.5-5.5% of middle-aged and elderly women. We have studied the heat and capsaicin receptor TRPV1, and its regulator nerve growth factor (NGF), in BMS. Patients with BMS (n=10) and controls (n=10) were assessed for baseline and post-topical capsaicin pain scores, and their tongue biopsies immunostained for TRPV1, NGF, and structural nerve markers neurofilament and peripherin. Nerve fibres penetrating the epithelium were less abundant in BMS (p<0.0001), indicating a small fibre neuropathy. TRPV1-positive fibres were overall significantly increased in BMS (p=0.0011), as were NGF fibres (p<0.0001) and basal epithelial cell NGF staining (p<0.0147). There was a significant correlation between the baseline pain score and TRPV1 (p=0.0143) and NGF fibres (p=0.0252). A significant correlation was observed between baseline and post-capsaicin pain (p=0.0006). Selective TRPV1 and NGF blockers may provide a new therapy for BMS.     

Anterior lumbar fusion using a hybrid interbody graft

Summary This is a radiographic report of 40 patients (20 men, 20 women) who underwent anterior lumbar interbody fusions (73 levels) utilizing a “hybrid” interbody graft composed of femoral cortical allograft (FCA) bone and iliac crest cancellous autograft bone. The average age at surgery was 38 years (range 17–64 years), and follow-up averaged 1.4 years (range 1.0–2.4 years). Nineteen of the patients had undergone previous lumbar surgery. Thirty-two patients (63 levels) underwent anterior fusion combined with some type of posterior fixation, and eight patients (10 levels) had no posterior fixation. Types of posterior fixation included: for 20 patients (36 levels) Steffee variable screw placement fixation, for 10 patients (23 levels) translaminar facet screws (TFS), for 1 patient (3 levels) Knodt rods and for 1 patient (1 level) facet screws. Based on the persistence of lucent lines at the graft-host interface, three patients (one level each) were felt to have non-unions at their latest follow-ups at 1.4, 1.5 and 2.0 years, respectively. Two of these patients had no posterior fixation, and the other had TFS fixation. The overall fusion rate was 96% (70 of 73 levels). The fusion rate for all levels treated with posterior fixation was 98% compared with 75% for those without fixation. Intervertebral disc heights (IVDH) were measured on all films and corrected for magnification with computer assistance. On average, the IVDH was increased postoperatively but returned to preoperative values at follow-up. IVDH loss was independent of the type of instrumentation used. No complications arose from the use of the hybrid graft. Incorporation of the allograft portion of the graft is slow and was felt to be complete in only 7 of the 73 levels at follow-up. We conclude that the hybrid interbody graft technique is a safe and reliable method for performing anterior lumbar interbody fusions and should be combined with some type of posterior fixation. Long-term follow-up will be required to assess the behaviour of the allograft until incorporation is complete.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

Capillary filtration in venous hypertension. Comparison between the vacuum suction chamber (VSC) device and straingauge phlethysmography.

To evaluate capillary filtration a group of normal subjects and two groups of subjects with venous incompetence (50 with deep and 50 with superficial incompetence) were studied with the vacuum suction chamber (VSC) device applied onto the internal perimalleolar region. This method was compared with straingauge plethysmography rate of ankle swelling (RAS). By the VSC the time taken for the weal to disappear (VSC time) was considered indicative of capillary filtration. The values obtained with the two methods were well related (r < 0.742) and there was a good separation between patients and normals. The separation between the two groups of patients was significantly better (p < 0.05) with the VSC time. In conclusion VSC time is a good indication of capillary filtration in comparison with straingauge plethysmography RAS. It may be used to assess variations in capillary filtration in venous hypertension and possibly to follow up the effects of treatments.