Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors.

BACKGROUND: Long-term intra-oesophageal acid suppression with proton pump inhibitors represents a management option for Barrett's oesophagus and severe reflux oesophagitis, but its stability over time has not been adequately assessed. AIM: Our aim was to evaluate prospectively the efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity after 2-year continuous treatment. METHODS: Forty-five patients with Barrett's oesophagus or severe reflux oesophagitis on a proton pump inhibitor regimen (once or twice daily) that normalised the total percentage acid exposure time were re-evaluated by means of 24-h oesophageal pH-monitoring after 2-year of continuous unmodified treatment. RESULTS: A significant rise in the total percentage acid exposure time was observed at 2-year follow-up (P=0.029), owing to an increased value in 27 (60%) cases (9 on a twice daily regimen), higher than normal in 10 of them (22% of the whole group) (3 on a twice daily regimen). In 18 patients (40%) the total percentage acid exposure time was stable or decreased. Heartburn remained efficiently suppressed in all patients. CONCLUSIONS: The efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity during continuous treatment may decrease over time, up to abnormal levels of oesophageal acid exposure in a minority of cases. This may occur without heartburn recurrence and with both once and twice daily regimens.

Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?

BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole.

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.

Pathophysiological characteristics of patients with non-erosive reflux disease differ from those of patients with functional heartburn.

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.

Extracellular levels of amino acids and choline in human high grade gliomas: an intraoperative microdialysis study.

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.

Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non-erosive reflux disease.

BACKGROUND: 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.

Effective intra-oesophageal acid suppression in patients with gastro-oesophageal reflux disease: lansoprazole vs. pantoprazole.

BACKGROUND: : Effective intra-oesophageal acid suppression is an important therapeutic goal in complicated and atypical gastro-oesophageal reflux disease. AIM: : To compare the efficacy of lansoprazole and pantoprazole in normalizing oesophageal acid exposure. METHODS: : Fifty patients with complicated or atypical gastro-oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole (n = 26) or 40 mg pantoprazole (n = 24) once daily. Three to four weeks after the start of treatment, patients underwent 24-h oesophageal pH monitoring whilst on therapy. If the results were improved but still abnormal, the dosage was doubled and pH monitoring was repeated. If oesophageal acid exposure was not improved, the patient was shifted to the alternative drug regimen. RESULTS: : Oesophageal acid exposure was normalized in all 26 patients treated with lansoprazole (in 35% of cases with a double daily dosage), whereas in six of the 24 (25%) patients treated with pantoprazole it was neither normalized nor lowered (P = 0.008). Accordingly, the mean percentage acid reflux time was significantly lower for the lansoprazole group (2.1) than for the pantoprazole group (5.8) (P = 0.032). CONCLUSIONS: : Effective intra-oesophageal acid suppression can be accomplished more reliably with lansoprazole than with pantoprazole in patients with complicated and atypical gastro-oesophageal reflux disease.

Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression.

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.

Laparoscopic fundoplication versus lansoprazole for gastro-oesophageal reflux disease. A pH-metric comparison.

BACKGROUND: Treatment strategies that abolish abnormal reflux could prevent long-term complications of gastro-oesophageal reflux disease. AIMS: To compare the efficacy of laparoscopic fundoplication and lansoprazole in abolishing abnormal reflux in patients with gastro-oesophageal reflux disease. PATIENTS: Study population comprised 130 patients referred for possible antireflux surgery and with heartburn as the dominant symptom. METHODS: After oesophageal manometric and pH-metric evaluation and detailed information 55 patients asked to undergo laparoscopic antireflux surgery while 75 chose a medical treatment regimen based on lansoprazole. Treatment efficacy was assessed by ambulatory oesophageal pH-monitoring. RESULTS: All 55 patients who underwent fundoplication became free of heartburn: oesophageal pH-monitoring gave normal results in 85%. In patients treated with lansoprazole, at individualized daily dosages titrated to abolish both heartburn and abnormal acid reflux, normal pH-metric results were obtained in 96% of cases (p<0.05 vs surgically treated patients). CONCLUSIONS: Lansoprazole at individualized dosages was significantly more effective than laparoscopic fundoplication, in the short-term, in abolishing abnormal reflux in gastro-oesophageal reflux disease patients.

Lansoprazole vs. omeprazole for gastro-oesophageal reflux disease: a pH-metric comparison.

BACKGROUND: Lansoprazole and omeprazole are widely used proton pump inhibitors for the management of gastro-oesophageal reflux. Normalization of oesophageal acid exposure is an important goal in the management of complicated and atypical gastro-oesophageal reflux disease. AIM: To compare the efficacy of lansoprazole and omeprazole in the abolition of abnormal reflux as assessed by oesophageal pH monitoring. METHODS: Seventy patients with complicated or atypical gastro-oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole or 20 mg omeprazole 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 proton pump inhibitor dosage was doubled and 24-h pH-metry was repeated after 20-30 days. RESULTS: Thirty-six patients were randomized to receive lansoprazole and 34 patients to receive omeprazole. Ten of the 36 (29%) patients treated with 30 mg lansoprazole once daily and 23 of the 34 (68%) patients treated with 20 mg omeprazole once daily had persistently abnormal reflux at oesophageal pH monitoring (P < 0.001). In all such cases, repeat pH monitoring after doubling the proton pump inhibitor dosage gave normal results. CONCLUSIONS: At the currently marketed dosages of lansoprazole and omeprazole, normalization of oesophageal acid exposure in patients is accomplished more easily with lansoprazole.

[Chronic osteomyelitis: a new therapeutical idea] / Osteomielite cronica: una nuova idea terapeutica.

We studied the case of a male patient aged 43 affected by post-traumatic chronic osteomyelitis with frequent relapses. Having supposed an insufficiency of the arterial and venous microcirculation in perilesional bone and soft tissue we decided for a therapy with iloprost and antibacterial drugs. After 15 months of treatment the patient hasn't showed any clinically evident relapsing episodes and we have not reported any side effects related to the therapy.

Probabilistic regularization in inverse optical imaging.

The problem of object restoration in the case of spatially incoherent illumination is considered. A regularized solution to the inverse problem is obtained through a probabilistic approach, and a numerical algorithm based on the statistical analysis of the noisy data is presented. Particular emphasis is placed on the question of the positivity constraint, which is incorporated into the probabilistically regularized solution by means of a quadratic programming technique. Numerical examples illustrating the main steps of the algorithm are also given.

The experimental Alzheimer drug phenserine: preclinical pharmacokinetics and pharmacodynamics.

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.

Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study.

Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage.

Choroid plexus papilloma of the cerebellopontine angle: a twelve patient series.

BACKGROUND: Choroid plexus papillomas (CPPs), of the cerebellopontine angle (CPA), are a rare entity and no surgical series have been reported so far. We reviewed all the pertinent literature of 12 patients operated on in the last 20 years at our institution. METHODS: All the patients were adults, ranging from 19 to 61 years. The group included 6 males and 6 females. Preoperatively, on computerized tomography (CT) (n = 10) or magnetic resonance imaging (MRI) (n = 4), differential diagnosis was difficult to achieve, especially with meningiomas. Hydrocephalus was disclosed in 8 cases. Angiography (n = 11) showed tumor blush with typical vascular supply in almost half the cases. RESULTS: In 6 patients a midline approach via the cerebellomedullary fissure was used; in the remaining 6 patients the retromastoid route was adopted. We found 2 "unconnected" tumors; no hilum was identified at surgery. Total tumor removal was achieved in 6 patients, predominantly in the last cases. Two patients died in the postoperative period, 3 patients had mild additional deficits, whereas 7 patients were stable or improved. All the patients were followed up for a mean period of 8.2 years. Conventional radiotherapy was carried out in 5 patients; 1 of them after tumor recurrence. Stereotactic radiotherapy was performed in 3 patients; 2 of them after recurrences. Two patients showed tumor progression and died during the follow-up. One of them presented a suprasellar metastasis and died much earlier (2 versus 7 years). CONCLUSION: Careful assessment and surgical planning is accomplished with the combined information from CT, MRI, and angiography. Typical characteristics are the following: vascular supply from the choroidal arteries, ventral extension, adhesion to the brainstem, and lower cranial nerves. Nowadays, total removal of CPPs of the CPA can be achieved with acceptable morbidity and mortality. In our experience, conventional radiotherapy did not prove effective.

In vivo imaging of cortical membrane remodeling in rats with chronic unilateral ablation of nucleus basalis magnocellularis: use of radiolabeled palmitic acid.

Membrane remodeling was imaged in vivo in brains of rats with a 2-week-old right-sided ablation of the nucleus basalis magnocellularis (NBM). To do this, [9,10-3H]palmitic acid ([3H]PAM) was injected intravenously and regional brain incorporation k* of tracer was determined with quantitative autoradiography after 20 min circulation. In NBM-lesioned animals, k* was elevated significantly (by up to 17%) in 11 ipsilateral frontal or parietal cortical regions, more so in layer 1 than in layers IV and V. Unoperated animals showed no right-left difference in k*, whereas sham-operated animals showed some unilateral effects of damage due to the needle track. Circulating [3H]PAM is incorporated into sn-1 positions of brain phospholipids, mainly phosphatidylcholine, and its rate of turnover is thought to reflect turnover of neuronal and glial membranes. These results, when related to published evidence of altered cortical phospholipid metabolism in NBM-lesioned rats, suggest that images of increased [3H]PAM incorporation into ipsilateral cortex reflect increased membrane remodeling involving phospholipids.

Effects of ethanolamine (Etn) administration on Etn and choline (Ch) levels in plasma, brain extracellular fluid (ECF) and brain tissue, and on brain phospholipid levels in rats: an in vivo study.

The sources and fates of brain ethanolamine (Etn) are poorly known and the effects of its administration have not been investigated, even though cortical levels are known to be reduced in certain neurodegenerative diseases. We studied the effect of different Etn doses (10(-3), 5 x 10(-3) and 10(-2) mol/kg, i. p.) on its and choline's (Ch) levels in arterial plasma and brain extracellular fluid (ECF) of awake rats. We also studied its effects on brain levels of Etn, Ch, and their respective major phospholipids. Etn administration caused dose dependent increases in Etn levels within both plasma and brain ECF. For the 10(-2) mol/kg dose, Etn levels were significantly (p<0.01) greater than pre-injection values in both the plasma and ECF. Whole brain Etn and phosphatidylethanolamine were also significantly (p<0.05) increased by 10(-2) mol/kg Etn. Exogenous Etn significantly (p<0.05) increased Ch levels in plasma and whole brain; Etn also increased brain ECF Ch levels. Our data show for the first time that circulating Etn can act as a source of brain Ch. Metabolic pathways that might mediate the increases in Etn and Ch are discussed, as are possible mechanisms of the decreases in brain Eth seen in Alzheimer's disease.

The long history of a cerebello-pontine angle epidermoid tumour--a case report and lessons learned.

The authors present the case of a patient accurately diagnosed and operated on for an epidermoid cyst in the CPA region, 30 years after the clinical onset with the initial symptom of hypoacusis. At the time of the operation, the patient presented with advanced CPA syndrome, and the tumour had grown to an enormous size. Complete capsule removal was not attempted due to its tenacious adherence to vital neurovascular structures. Thirteen years after surgery, the patient underwent a second operation due to tumour regrowth. The case provides supporting evidence that the clinical findings of a CPA epidermoid cyst may be minimal, and remain so for extended periods of time until the tumour has spread widely. Epidermoids tend to insinuate in the cisterns around cranial nerves, blood vessels, and the brainstem, rather than compressing these structures. The importance of early detection and radical removal, presently facilitated by Magnetic Resonance Imaging, is emphasized.