Vincenzo Frusciante

Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia

BACKGROUND & AIMS Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported. METHODS Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed. RESULTS One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia. CONCLUSIONS Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer.

Gastrointestinal motor dysfunction, symptoms, and neuropathy in noninsulin-dependent (type 2) diabetes mellitus

Although relatively frequent. diabetic involvement of digestive tract motility has not been investigated extensively in different organs. The authors studied esophageal, gastric, and gallbladder motor function in 35 type 2 (noninsulin-dependent) diabetic patients to determine the extent of gut involvement. Of these patients, 27 (77%) had peripheral neuropathy, 12 (34%) had both peripheral and autonomic neuropathy, and 22 (63%) had gastrointestinal symptoms. Esophageal manometric abnormalities were recorded in 18 patients, and delayed radionuclide emptying of the esophagus was documented in 16 patients, with a 83% concordance between the two tests. Scintigraphic gastric emptying of solids was delayed in 56% of patients, whereas gallbladder emptying after cholecystokinin stimulation was reduced in 69% of them. In 74% of patients at least one of the viscera under investigation showed abnormal motor function; however, only 36% of patients displayed involvement of the three organs. Gastrointestinal symptoms, duration and therapy of diabetes, previous poor glycemic control, and retinopathy did not correlate with the presence or the extent of motor disorders. Neuropathy was not predictive of gastrointestinal involvement and its extent; however, when motor abnormalities were present in patients with neuropathy, these were usually more severe. Gastrointestinal motor disorders are frequent and widespread in type 2 diabetics, regardless of symptoms. Autonomic neuropathy has a poor predictive value on motor disorders (0.75 for the esophagus, 0.5 for the stomach, 0.8 for the gallbladder), thus suggesting the coexistence of other pathophysiologic mechanisms.

Skeletal involvement in female acromegalic subjects : The effects of growth hormone excess in amenorrheal and menstruating patients

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty‐two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy‐terminal propeptide of type I collagen (PICP), serum type I cross‐linked N‐telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D‐Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X‐ray absorptiometry both at lumbar spine and at three femoral sites (Wards triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D‐Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohns disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohns disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohns disease and in those with colonic involvement. This may have therapeutic implications.

Regulation of PTH secretion by 25-hydroxyvitamin D and ionized calcium depends on vitamin D status: a study in a large cohort of healthy subjects

INTRODUCTION Previous papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered. DESIGN Cross-sectional. MATERIALS AND METHODS In 1050 healthy men (547) and women (503), serum ionized calcium (iCa), creatinine (Cr), albumin, 25OHD, and PTH were measured. After conventional analysis, a regression tree was fitted on the data set. RESULTS 25OHD and PTH values showed significant opposite seasonal changes. 25OHD levels negatively correlated with PTH, which in turn negatively correlated with iCa. A regression tree was fitted to the whole data set using PTH as the response variable and 25OHD and iCa as covariates. PTH concentration depended on that of iCa only in subjects with 25OHD levels>16.35 ng/mL, while for 25OHD<16.35 ng/mL it depended on 25OHD values. CONCLUSIONS Our results indicated that PTH levels were highly conditioned by those of 25OHD in subjects with 25OHD values lower than 16.35 ng/mL and by those of iCa only for higher 25OHD concentration.

Gallbladder function and gastric liquid emptying in achalasia

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4%±30.4 vs 80.3±8.3 of controls, mean±sd,P=0.007) and a slower than normal ejection phase (9.1%/min±6.6 vs 18.1±4.5,P=0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min±15.4 vs 74.7 min±11.5 in the controls (P=0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative changes of extraesophageal nerve fibers as well as their clinical significance require further investigations.

Hepatic hydrothorax. Diagnosis and management.

Twelve cases of right hepatic hydrothorax are reported. Tc-99m SC that was injected intraperitoneally and intrapleurally provided evidence of a one-way flow of fluid from the peritoneal to the pleural cavity. Eight patients, whose hydrothorax was refractory to sodium restriction, diuretics and repeated thoracenteses, were treated by endopleural tetracycline instillation. The pathogenetic role of the diaphragmatic defect and the diagnostic usefulness of radionuclide imaging are stressed.

Assessment of Serum Total and Bone Alkaline Phosphatase Measurement in Clinical Practice

Abstract The aim of the study was to measure serum levels of the bone-specific isoenzyme of alkaline phosphatase in normal subjects and patients with metabolic bone disease by using an immunoadsorption assay. We studied 140 healthy adults, 122 patients affected by metabolic bone disease and 15 patients with cholestatic liver disease. Mean values of the bone-specific isoenzyme of alkaline phosphatase in healthy men were significantly higher than those found in premenopausal women (17.8 ± 4.2 U/l vs 15.6 ± 4.6 U/l, p<0.02); postmenopausal women had significantly higher levels of bone-specific isoenzyme of alkaline phosphatase (22.6 ± 6.4 U/l) than premenopausal women (p<0.0001). After the menopause total alkaline phosphatase increased by 46 %, while the increase in bone-specific isoenzyme of alkaline phosphatase was 39 %. No significant correlations were found between bone-specific isoenzyme of alkaline phosphatase and either age or years since menopause, in postmenopausal subjects. In patients with bone-specific isoenzyme of alkaline phosphatase above the upper limit of normal, the assay had a sensitivity of 100 % only in patients with Pagets disease of bone. In patients with cholestatic liver disease we found no correlation between bone-specific isoenzyme of alkaline phosphatase and either total alkaline phosphatase and γ-glutamyl transpeptidase, while a positive correlation was found between total alkaline phosphatase and γ-glutamyl transpeptidase. Our results confirm the role of bone-specific isoenzyme of alkaline phosphatase assay in clinical research; however, its usefulness in clinical practice is unclear once liver involvement has been excluded.

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients

BackgroundSomatostatin (SS) acts as a universal endocrine off-switch, and also inhibits the growth of neuroendocrine tumours through its specific receptors (SSTRs). Somatostatin receptors are G-protein-coupled receptors, which are encoded by five separate genes (SSTR1-5). Short peptide analogues demonstrate specific binding only for the subgroup consisting of SSTR2a, SSTR3 and SSTR5. Moreover, previous studies reported that expression of mRNA for SSTR2a correlated with therapeutic outcome in patients with carcinoid tumours treated with somatostatin analogs.PurposeTo develop and apply a Real Time Quantitative PCR technique (RT-qPCR) to compare and contrast the mRNA levels of SSTR2a, SSTR3 and SSTR5 in Neuroendocrine Lung Cancer affected patients.MethodsPeripheral blood samples from 21 neuroendocrine lung cancer affected patients (14 SCLC, 6 LC and 1 LCNEC) subjected to scintigraphy with 111In-DTPA-D-Phe1-octreotide (OctreoScan) and 24 healthy blood donors were investigated by RT-qPCR. mRNA levels for SSTR2a, SSTR3 and SSTR5 were measured in peripheral blood samples with a relative quantification method using plasmid dilutions as calibration curves and GAPDH as reference gene.ResultsA statistically significant increase in target genes/GAPDH copy number ratio was found for SSTR2a (median 38; IQR 22–141) and SSTR5 (median 51; IQR 19–499) in neuroendocrine lung cancer affected patients as compared with samples from healthy blood donors (P ≤ 0.0003 and P ≤ 0.0005). Since low levels of expression were detected in the control group for all three genes, optimal cut-off values were assessed using ROC curve analyses and were equal to 9.05 for SSTR2a and 16.97 for SSTR5. These cut off values resulted in a sensitivity of 86% (95%IC 65–95) for both markers and a specificity of 83% (95%IC 64–93%) and 79% (95%IC 60–91%) for SSTR2a and SSTR5 respectively. Comparison between OctreoScan results and RT-qPCR analysis demonstrated agreement in 76% of the cases.ConclusionsOur results suggest that SSTR2a and SSTR5 mRNAs are detectable in peripheral blood of neuroendocrine lung cancer affected patients using real-time quantitative PCR, with a good agreement with OctreoScan. The high sensitivity of this non-invasive molecular technique suggests that this method could represent a useful tool in the clinical management of neuroendocrine lung cancers.