By exploiting the analyticity and boundary value properties of the thermal Green functions that result from the KMS condition in both time and energy complex variables, we treat the general (non-perturbative) problem of recovering the thermal functions at real times from the corresponding functions at imaginary times, introduced as primary objects in the Matsubara formalism. The key property on which we rely is the fact that the Fourier transforms of the retarded and advanced functions in the energy variable have to be the "unique Carlsonian analytic interpolations" of the Fourier coefficients of the imaginary-time correlator, the latter being taken at the discrete Matsubara imaginary energies, respectively in the upper and lower half-planes. Starting from the Fourier coefficients regarded as "data set", we then develop a method based on the Pollaczek polynomials for constructing explicitly their analytic interpolations.

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SummaryBackground : The reason why less than one‐half of patients with gastro‐oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking.Aim : To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease.Methods : Ambulatory 24‐h oesophageal pH monitoring was performed in 220 patients with gastro‐oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non‐erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated.Results : The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non‐erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time.Conclusions : Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro‐oesophageal reflux disease.

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The concentrations of endogenous amino acids and choline in the extracellular fluid of human cerebral gliomas have been measured, for the first time, by in vivo microdialysis. Glioblastoma growth was associated with increased concentrations of choline, GABA, isoleucine, leucine, lysine, phenylalanine, taurine, tyrosine, and valine. There was no difference between grade III and grade IV tumors in the concentrations of phenylalanine, isoleucine, tyrosine, valine, and lysine, whereas the concentrations of choline, aspartate, taurine, GABA, leucine, and glutamate were significantly different in the two tumor-grade subgroups. In contrast to the other compounds, the concentration of glutamate was decreased in glioma. The parenchyma adjacent to the tumor showed significant changes only in the extracellular concentration of glutamate, isoleucine, and valine. The concentrations of choline and the amino acids, glutamate, leucine, taurine, and tyrosine showed significant positive correlations with the degree of cell proliferation. Epilepsy, which is relatively common in subjects with gliomas, was shown to be a significant confounding variable when the extracellular concentrations of aspartate, glutamate and GABA were considered.

Phenserine, a phenylcarbamate of physostigmine, is a new potent and highly selective acetylcholinesterase (AChE) inhibitor, with a >50‐fold activity versus butyrylcholinesterase (BChE), in clinical trials for the treatment of Alzheimer's disease (AD). Compared to physostigmine and tacrine, it is less toxic and robustly enhances cognition in animal models. To determine the time‐dependent effects of phenserine on cholinergic function, AChE activity, brain and plasma drug levels and brain extracellular acetylcholine (ACh) concentrations were measured in rats before and after phenserine administration. Additionally, its maximum tolerated dose, compared to physostigmine and tacrine, was determined. Following i.v. dosing, brain drug levels were 10‐fold higher than those achieved in plasma, peaked within 5 min and rapidly declined with half‐lives of 8.5 and 12.6 min, respectively. In contrast, a high (>70%) and long‐lasting inhibition of AChE was achieved (half‐life >8.25 h). A comparison between the time‐dependent plasma AChE inhibition achieved after similar oral and i.v. doses provided an estimate of oral bioavailability of 100%. Striatal, in vivo microdialysis in conscious, freely‐moving phenserine‐treated rats demonstrated >3‐fold rise in brain ACh levels. Phenserine thus is rapidly absorbed and cleared from the body, but produces a long‐lasting stimulation of brain cholinergic function at well tolerated doses and hence has superior properties as a drug candidate for AD. It selectively inhibits AChE, minimizing potential BChE side effects. Its long duration of action, coupled with its short pharmacokinetic half‐life, reduces dosing frequency, decreases body drug exposure and minimizes the dependence of drug action on the individual variations of drug metabolism commonly found in the elderly.

Summary Background : Patients with endoscopy‐negative heartburn can be subdivided into non‐erosive reflux disease and functional heartburn on the basis of abnormal and normal, respectively, oesophageal acid exposure. Different pathophysiological characteristics could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn. Aim : To assess if non‐erosive reflux disease and functional heartburn are pathophysiologically distinguishable. Methods : Oesophageal manometry and pH‐monitoring were performed in 145 patients with endoscopy‐negative heartburn, in 72 patients with erosive reflux disease, in 58 patients with complicated reflux disease, and in 60 controls. Results : Patients with non‐erosive reflux disease (84 cases) and functional heartburn (61 cases) differed with regard to the prevalence of hiatal hernia (49% vs. 31%, P = 0.008), the mean lower oesophageal sphincter tone (18.5 vs. 28.4 mmHg, P < 0.05), and the number of upright diurnal acid refluxes lasting more than 5 min (3.6 vs. 0.37, P < 0.05). The results were very close in thenon‐erosive reflux disease, erosive reflux disease and complicated reflux disease groups, whilst patients with functional heartburn were indistinguishable from controls. Conclusions : Pathophysiological characteristics typical of gastro‐oesophageal reflux disease are found in patients with non‐erosive reflux disease but not in patients with functional heartburn. This could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn and suggests considering different management strategies.

Background: Effective intra‐oesophageal acid suppression can be achieved with lansoprazole. The daily dosage could be influenced by the presence of hiatal hernia. Aim: To assess the lansoprazole daily dosage required to normalize oesophageal acid exposure in patients with and without hiatal hernia. Methods: Fifty patients with complications or atypical manifestations of gastro‐oesophageal reflux disease were given lansoprazole, 30 mg once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the lansoprazole dosage was doubled and 24‐h pH‐metry was repeated 20–30 days thereafter. Results: A 30‐mg daily dosage of lansoprazole normalized oesophageal acid exposure in 70% of cases, whilst a 60‐mg daily dosage was necessary in the remainder: the two groups differed only in the presence of hiatal hernia (28% vs. 100%, respectively; P=0.000). Effective intra‐oesophageal acid suppression was obtained in all 25 patients without hiatal hernia with the 30‐mg daily dosage of lansoprazole. Conclusions: Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra‐oesophageal acid suppression in complicated and atypical gastro‐oesophageal reflux disease. High efficacy of a 30‐mg daily dosage of lansoprazole can be predicted in the absence of hiatal hernia.