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Biomedical subjects

S A Raptis

Publications and source records attributed to S A Raptis.

At least 91 records · Page 5Linked to original sources

The clinical need for sphincter of Oddi manometry in gastrointestinal endoscopy units.

The clinical need for sphincter of Oddi manometry (SOM) was investigated by retrospective analysis of 736 consecutive endoscopic retrograde cholangiopancreatography (ERCP) referrals (1985-89). During this period SOM was not performed in any unit in Greece including our own. Assuming a conservative or a more liberal policy in the utilization of SOM, a biliary and a pancreatic group of patients were established respectively, depending on the clinical presentation. ERCP was diagnostic in 168/194 (86.6%) of patients referred for post-cholecystectomy symptoms, but SOM was considered to be necessary to establish a diagnosis in the remaining 26 (13.4%) patients (biliary group). ERCP revealed pancreatic and/or biliary pathology in 46/69 (66.7%) patients, referred for symptoms attributed to pancreatitis, but 11/69 (15.9%) patients with pancreas divisum and 12/69 (17.4%) with acute recurrent idiopathic pancreatitis may have benefitted from SOM for planning endoscopic therapy (pancreatic group). Thus, only 5 patients from each group per 147 ERCP annual referrals were candidates for SOM. When taking into account that to run a SOM service the minimum annual number of investigations should be 50 and that the provision of ERCP in the UK is 50 per 100,000 of population per year, it is extrapolated that such a Gastrointestinal Endoscopy Unit should serve a population of 1.5 to 3 million.

Aged↗

Complex carbohydrate malabsorption in exocrine pancreatic insufficiency.

The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase < or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p < 0.001). The number of patients with fat (> 7 g, n = 8) or carbohydrate (increase in H2 > or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p < 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat.

Adult↗

Pancreatic duct width: its significance as a diagnostic criterion for pancreatic disease.

The significance of main pancreatic duct width in the diagnosis of pancreatic disease, was studied in 338 endoscopic retrograde pancreatographies. Two hundred and forty patients referred for suspected biliary disease had normal pancreatograms (Group 1), 60 had pancreatic carcinoma (Group 2) and 38 had a history and pancreatogram compatible with chronic pancreatitis (Group 3). After categorizing patients by decade, in group 1 the effect of aging on the pancreatic duct width in the head, body and tail (F5,234 > 3.71, p < 0.003) was pronounced, especially after the fifth decade. There was a significant difference between groups 1, 2 and 3 in terms of the width of the main pancreatic duct in all three parts of the pancreas (F2,325 > 42.24, p < 0.001). The upper range of normal pancreatic duct width was 8.0 mm, 4.0 mm and 2.4 mm in the head, body and tail, respectively. Abnormal ductograms were wider than the normal ranges in the head, body and tail of the pancreas in 14%, 49% and 59% (p < 0.001) of the patients, respectively. Establishing normal ranges of the pancreatic duct width may help in the diagnosis of pancreatic disease. Measurements in the body and tail, as compared with the head, are a more sensitive indicator of pancreatic duct dilation.

Adult↗

Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans.

The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.

1-Deoxynojirimycin↗

Pulsatile human corticotropin-releasing hormone prevents dexamethasone-induced suppression of the plasma cortisol response to hypoglycemia in normal men.

Insulin-induced hypoglycemia causes a sequential stimulation of all three components of the hypothalamic-pituitary-adrenal axis. States of acute glucocorticoid excess, such as the overnight (1 mg) dexamethasone suppression test (DST), inhibit both the basal cortisol level and the response to an insulin tolerance test (ITT). However, whether this negative feedback effect is exerted primarily at the hypothalamic or the pituitary level is not clear. To explore this question further we have examined the cortisol response to insulin-induced hypoglycemia in three experimental settings, in the following order: 1) a control ITT performed at 0900 h after an overnight hospital stay (cITT); 2) an ITT at 0900 h after oral dexamethasone, 1 mg, at 2300 h on the previous evening (DST + ITT); and 3) an ITT at 0900 h after dexamethasone, 1 mg, at 2300 h and hCRH, 1 microgram/kg iv, at 90 min intervals from 0100-0700 h (DST+hCRH + ITT). The response to ITT was defined as the peak cortisol increment (peak minus baseline). Since the study objective was to test whether overnight pulsatile hCRH could prevent dexamethasone-induced suppression of the response to a morning ITT, only subjects that demonstrated a greater than 25% decrease in the cortisol response to DST + ITT vs. cITT received the full protocol (five of nine normal men). Basal ACTH and cortisol secretion remained suppressed throughout the night during both the Dex + ITT and Dex + hCRH + ITT studies when compared to the control study (cITT, P < 0.05). However, the cortisol response to hypoglycemia during DST + hCRH + ITT was significantly greater than during DST+ITT (P < 0.05) and was similar to the cITT response. Thus, pulsatile hCRH, administered during the 10 h between dexamethasone and the subsequent hypoglycemic stimulus, prevented acute suppression by dexamethasone of the cortisol response to hypoglycemia. We conclude that the dexamethasone-induced inhibition of the cortisol response to hypoglycemia results primarily from suppression by dexamethasone of basal hypothalamic corticotropin-releasing factor and the consequent impairment of corticotroph responsiveness to exogenous and endogenous corticotropin-releasing factor.

Adrenocorticotropic Hormone↗

Conservative treatment of acute pancreatitis: the use of somatostatin.

The aim of the medical treatment of acute pancreatitis is to rest the gland and to reduce complication and mortality rates. The effect of various treatment modalities on the course and outcome of acute pancreatitis have been disappointing. This review critically considers the results of reported therapeutic trials and our own unpublished data of somatostatin and its long-acting synthetic analogue, octreotide, in acute pancreatitis. It is concluded that somatostatin is a promising drug. It reduces pancreatic enzyme secretion, the clinical need for analgesic drug administration, and the local complication rate, and shortens hospitalization. However, its effect on mortality rates is questionable. It is suggested that large-scale, carefully designed studies of somatostatin are needed to evaluate the beneficial effect of this drug on the course and outcome of acute pancreatitis. Since most of the trials included pancreatitis of various etiologies, it is also suggested that cases of acute biliary pancreatitis should be excluded or evaluated separately, as these patients are best treated by endoscopic sphincterotomy.

Acute Disease↗

Proinsulin as a possible therapeutic agent.

Gene technology has made significant amounts of biosynthetic human proinsulin (BHP) for biological and clinical studies available. It has been shown both in vitro and in vivo that BHP is about 10% as active as biosynthetic human insulin. More specifically it is 8% as potent regarding its action in stimulating peripheral glucose disposal and 12% as potent in suppressing hepatic glucose output. Its hypoglycemic effect is rather produced by the intact molecule or its intermediates and not by conversion to insulin or C-peptide. BHP appears to exert a more prolonged action when administered subcutaneously compared to NPH insulin. Furthermore because of its weaker effect on peripheral glucose utilization it is expected to create less profound hypoglycemia. Under conditions of equipotency BHP may stimulate triglyceride synthesis in a lower degree and in that way be less lipogenic. On longterm basis BHP proved to have a low immunogenic potential. We investigated the efficacy of BHP in split doses in type II diabetics with relative insulin resistance. Glucose levels at 1600 and 2000 and 0400 hrs as well as integrated glycemia over the 24 h period were lower under BHP. The potency of BHP in this and other studies has been demonstrated after application of greater quantities from it in terms of equimolarity. Nevertheless there are certain features such as the protracted action, the stronger effect on hepatic glucose production and the lower suppression of endogenous insulin secretion which make proinsulin a promising agent in the future management of type II diabetes.

Diabetes Mellitus, Type 2↗

Increased platelet activity in diabetic macroangiopathy.

In order to investigate the relationship between the in vivo platelet activity and diabetic macroangiopathy we have measured plasma beta-thromboglobulin (beta-TG) concentrations by means of a very sensitive radioimmunoassay in 55 diabetics, aged 47-80 years, and in 27 non-diabetic healthy controls (group A) of respective age and sex. Among diabetics 17 were free of vascular complications (group B) in terms of diabetic micro- or macroangiopathy, while the remaining 38 (group C) suffered from peripheral occlusive arterial disease (POAD) of the lower limbs. All subjects underwent a thorough clinical and laboratory investigation. The diagnosis of POAD was based upon the findings of Doppler ultrasound examination and was confirmed by selective arteriography. The mean plasma beta-TG concentrations were significantly higher in the two groups of diabetics compared to the non-diabetic controls (p < 0.001), whereas the highest beta-TG levels were found in diabetics with POAD (py 0.001), (beta-TG: mean +/- 1 SD ng/ml; group A: 26.50 +/- 13.14; group B: 55.88 +/- 26.56; group C: 106.50 +/- 52.65). These findings reveal an increased release reaction of platelets in diabetics and an enhanced in vivo platelet activity especially in POAD subjects. However, this may occur not only in cases with prominent macroangiopathy but also in the early stages of diabetic angiopathy when the vascular lesions cannot be traced clinically.

Aged↗

Lactose maldigestion and milk intolerance in healthy Greek schoolchildren.

The prevalence of lactose maldigestion in Greek adults is 75% but the age at which the lactase activity starts declining is not known. The prevalences of lactose maldigestion and intolerance were investigated in 150 randomly selected Greek children 5-12 y old by using breath-hydrogen analysis after ingestion of lactose (2 g/kg body wt, maximum 50 g) or 0.240 L of milk. Prevalence of lactose maldigestion increased with age (y = -7.30 + 6.49x, r = 0.88, P = 0.004), being 29.4% and 80.0% at ages 5 and 12 y, respectively. Before testing, the reported prevalences of milk-related symptoms by children with high and low lactose-digestion capacity were 21.1% and 39.7% (chi 2 = 5.96, P = 0.015), respectively. However, the corresponding prevalences of lactose intolerance after ingestion of milk were 7.3% and 8.6% (chi 2 = 0.1, P = 0.72) and only three children had a delta H2 greater than or equal to 20 ppm postprandially. Although intestinal lactase activity declines before age 5 y and many Greek children report milk-related symptoms, true malabsorption and intolerance of lactose after a glass of milk is rarely seen at this age.

Age Factors↗

[Effect of starvation and phenobarbital on the activity of liver uroporphyrinogen synthetase].

Liver uroporphyrinogen synthetase activity was measured in 45 mice, divided in three groups. The mice of the 1st group served as controls, those of the 2nd starved for 24 hours, while those of the 3rd were injected intraperitoneally with phenobarbital. The enzymic activity was found significantly (p less than 0.001) lower in the animals of the 2nd group (17.49 +/- 2.25 nmol/g/h) and higher in those of the 3rd (25.82 +/- 3.73 nmol/g/h) as compared to the controls (20.89 +/- 2.11 nmol/g/h). If these effects also exist in the human it could be suggested that starvation may be doubly harmful for the patients with acute intermittent porphyria by aggravating both their enzymic disorders. On the contrary, in the case of phenobarbital its undesired effect on porphyria may be moderated by a simultaneous induction of the uroporphyrinogen synthetase.

5-Aminolevulinate Synthetase↗

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time.

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151 +/- 15 min and a lactulose transit time of 86 +/- 22 minutes (X +/- SD, P less than 0.001). The coefficient of variation of breakfast transit time (11.6 +/- 5.3%, range: 6.9-24.2%) was less than that of lactulose transit time (30.7 +/- 7.8%, range: 22.1-50.0%, P less than 0.001). In a second set of experiments, the liquid phase marker (99mTechnetium-diethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3 +/- 5.4) than after the breakfast (33.9 +/- 10.9 min, P less than 0.01) and MCTT was shorter after lactulose (77 +/- 32 vs 104 +/- 40 min, respectively, P less than 0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.

Adult↗

Efficacy of a new needleless insulin delivery system monitoring of blood glucose fluctuations and free insulin levels.

A new insulin delivery system Vitajet has been invented which involves a high-pressure spring and obviates the use of needle injections. To study its efficacy we compared blood glucose fluctuations, integrated glycemia, free insulin and total free insulin concentrations in six insulin-dependent diabetics. After obtaining a steady state of carbohydrate metabolism overnight by feedback control through the artificial endocrine pancreas (AEP) Biostator, the patients received their usual morning and evening doses of insulin by either conventional injection or Vitajet in random order. Blood glucose levels were significantly lower after Vitajet than conventional injections (p less than 0.04) between 10 a.m. and 4 p.m., but the difference disappeared from 4 p.m. onwards. The areas under the curve (AUCs) of glucose fluctuations were lower after Vitajet (28036 +/- 4655 vs 31086 +/- 2310 mg. min% mean +/- SEM, p less than 0.01). AUCs for free insulin concentrations (microU.min/ml) were close: 39286 +/- 4510 (Vitajet) vs 30597 +/- 3575 (conventional). It is concluded that Vitajet constitutes an efficient needleless route for administering insulin pulses.

Adolescent↗

The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas.

On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics.

Adult↗

Common cytogenetic findings in gastric cancer.

Cytogenetic analysis was performed in five cases of intestinal type gastric carcinoma. Three cases were near-diploid and two others were near-triploid. The chromosomes involved were: #9 (four cases), #8 (three cases), #1, and #7 (two cases each). The nonrandom chromosomal abnormalities included aberrations of chromosome #9 as trisomy or i(9q) or 9p+ marker chromosome and excess of 8q material (i.e., trisomy or i(8q) chromosome). Our results indicate that abnormalities of chromosome #9 are a common feature in a subgroup of intestinal type gastric cancers and that there are common cytogenetic abnormalities in gastric and large bowel cancer.

Adenocarcinoma↗