Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST).

BACKGROUND: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. METHODS: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. RESULTS: At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. CONCLUSIONS: Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men.

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.

Neurotensin-like immunoreactivities in human plasma: feeding responses and metabolism.

Feeding responses and day and night levels of plasma concentration of neurotensin (NT) and NT-fragments were studied in healthy subjects. Plasma levels were measured by three radioimmunoassays recognizing intact NT in addition to C- and N-terminal immunoreactivity. The metabolism of NT was studied following intravenous administration. In 106 subjects fasting levels of intact NT (median 18 pmol/l), C-terminal (median 30 pmol/l) and N-terminal immunoreactivity (median 95 pmol/l) were unrelated to sex or age. Postprandially plasma levels in seven subjects measured with all assays increased by a factor 1-3. Following a mixed meal the increase was biphasic, whereas the response to dairy cream was monophasic. Repetitive measurements during 24 hours showed that levels of N-terminal immunoreactivity fluctuated in a manner related to meal ingestion and were elevated throughout the daytime, whereas intact NT and C-terminal immunoreactivity changed little. Following intravenous infusion of 2.4 pmol/kg/min NT in 5 subjects the chromatographic pattern was similar to that seen postprandially. The plasma half life of intact NT and C-terminal immunoreactivity was 1.5 and 1.2 min, whereas that of N-terminal immunoreactivity was 10.0 min. The differences in circulating levels could be explained by these differences in metabolism, but the physiological significance remains to be elucidated.

Extraction of neurotensin-like immunoreactivities from porcine ileal mucosa.

The extractability of neurotensin (NT) from porcine ileal mucosa was studied by comparison of eight extraction procedures. Tissue content of neurotensin-like immunoreactivity was quantitated and characterized by sequence-specific radioimmunoassays and gel filtration chromatography. Homogenization prior to boiling in extraction solvent produced higher levels of the intact peptide than the reverse procedure. N-terminal immunoreactivity was not influenced by the sequence of these steps. Tissue levels of intact NT were highest after extraction with 2.0 M acetic acid (mean 79.1 pmol/g, N = 6) and lowest with distilled water (mean 6.5 pmol/g, N = 6). The opposite was the case with levels of N-terminal immunoreactivity (mean 55.2 pmol/g and 105.7 pmol/g respectively, N = 6). Recovery experiments with addition of synthetic NT 1-13 and the N-terminal fragment NT 1-8 indicated that these differences could be explained by differences in recovery of intact NT and N-terminal immunoreactive components in tissue. Gel chromatography confirmed that in acetic acid almost only the intact peptide was extracted from ileal mucosa, and showed that after extraction in water or phosphate buffer several N-terminal components were present. The results suggest that a molecular heterogeneity may be present in ileal tissue. If this concept is supported by further studies differential extraction procedures may be needed in the future.

Effect of neurotensin and neurotensin fragments on gastric acid secretion in man.

The effect of intravenous infusion of neurotensin (NT) and NT-fragments on pentagastrin stimulated gastric acid secretion was investigated in healthy subjects. Neurotensin was infused in three doses (72, 144 and 288 pmol/kg per h). An N-terminal fragment (NT 1-8), a C-terminal fragment (NT 8-13) and an NT-analogue, substituted at the C-terminal tyrosine residue (Phe11-NT) were infused in two doses (72 and 144 pmol/kg per h). Concentrations of the infused peptides were measured in peripheral venous blood by radioimmunoassay. Plasma levels of NT 1-13, NT 1-8 and Phe11-NT increased in a dose-dependent manner; NT 1-13 to 50 (34-69), 78 (54-113) and 143 (112-242) pmol/l (medians and range) at 72, 144 and 288 pmol/kg per h, NT 1-8 to 405 (340-465) and 1215 (915-1300) pmol/l, and Phe11-NT to 200 (110-245) and 390 (250-410) pmol/l at 72 and 144 pmol/kg per h, respectively. Increases in plasma levels of NT 8-13 could not be detected during the infusion, suggesting that the fragment is rapidly metabolized in man. Neurotensin 1-13 inhibited gastric acid secretion in a dose-dependent manner and the decrease in gastric acid secretion was linearly related to plasma levels of NT 1-13. Neurotensin 1-8 and NT 8-13 inhibited gastric acid secretion only at 144 pmol/kg per h, while the analogue Phe11-NT had no effect. The results showed that the inhibition of gastric acid secretion produced by NT was dose-dependent and linearly related to circulating levels of NT, and that under physiological conditions this effect presumably is elicited by the C-terminal part of the peptide.

Secretion of neurotensin from isolated perfused porcine ileum.

The secretion and molecular nature of immunoreactive neurotensin (NT) was studied following stimulation of an isolated perfused porcine ileal segment with glucose, triglyceride and intra-arterial infusion of gastrin-releasing peptide (GRP). Secreted peptides were separated using gel chromatography and analyzed with 3 sequence-specific radioimmunoassays towards NT. Glucose (5%) and GRP both stimulated NT secretion from the ileal segment whereas pure triglyceride did not. Maximal secretion of NT during glucose perfusion was 0.448 nmol/min and 6.9 nmol/min during GRP infusion (medians, n = 5). GRP infused in doses from 10(-10) to 10(-8) M stimulated NT release in a dose-related manner. Following gel chromatography only the intact peptide and no smaller or larger molecular size immunoreactive components were observed. The study showed that both luminal and humoral stimuli release NT from the isolated pig ileum. Apparently no fragments or other NT-related immunoreactive components were cosecreted with the peptide.

The effect of calcium on hyperoxaluria following jejunoileal bypass in morbid obesity.

In order to investigate the effect on urinary oxalic acid excretion, ten patients with jejunoileostomy for morbid obesity were treated with oral calcium. We found a statistically significant decrease. The investigation suggests that the oral administration of calcium alone is not sufficient, in a dosage of 900 mg daily, to normalize the urinary oxalate excretion. The indications for calcium therapy in this group of patients is discussed.

Serum gastrin and blood glucose levels in gastroplasty for morbid obesity.

Fasting and meal-stimulated serum gastrin and glucose levels were measured in 11 patients before and 3 months after gastroplasty for morbid obesity. Overall blood glucose levels were significantly reduced after surgery (P less than 0.05), whereas the response to a meal was not influenced to any significant degree (P greater than 0.10). The fasting serum gastrin level was not significantly influenced by gastroplasty (P greater than 0.10). Postprandial serum gastrin increased significantly independent of gastroplasty (P less than 0.001). The presence of a marginally significant (0.10 greater than P greater than 0.05) interaction between postprandial gastrin levels and operation raises the possibility that gastroplasty additionally increases the postprandial serum gastrin level.

Neurotensin inhibits meal-stimulated gastric acid secretion in man.

The effect of physiological doses of exogenous neurotensin on meal-stimulated gastric acid secretion and serum gastrin concentration was investigated in six healthy subjects. Acid secretion was reduced by 32% during intravenous infusion of neurotensin, the plasma neurotensin concentration being within physiological range. Serum gastrin concentration was unchanged during infusion of neurotensin. The results strongly suggest that neurotensin participates in the regulation of gastric acid secretion and support the theory that neurotensin may play a role in the intestinal phase of gastric acid secretion in man.

Inhibition of gastric acid secretion by jejunal glucose and its relation to osmolality and glucose load.

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.