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Biomedical subjects

S Doran

Publications and source records attributed to S Doran.

At least 19 recordsLinked to original sources
PubMed2005

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Adult↗
PubMed2003

Ultrastructure of the seminiferous tubules in human testes before and after varicocelectomy.

Ultrastructure of the membrana propria and the seminiferous epithelium was studied in infertile human testis both before and 3-6 months after varicocelectomy. The frequent alterations, observed before and after the operation, were extremely thickened membrana propria, deep invaginations, multilamination and knob-like formation of basal laminae and formation of multinucleated spermatids, which were all considered as the common response of the testis to different noxious agents. Although the cells of the seminiferous epithelium were clearly affected by varicocele before varicocelectomy, many areas exhibited normal features after the operation. Furthermore, multinucleated cells, sharing common features of Sertoli cell and spermatogonium, were observed, as well as presence of well-developed annulate lamellae in the Sertoli cells, exhibiting centrioles in the vicinity of their nuclei after varicocelectomy. These multiple ultrastructural observations indicate that Sertoli cell division takes place. This study suggests that if the observation period of the tissue samples after varicocelectomy is long enough, the reversible changes of the tubular cells would be seen much more frequently.

Adult↗
PubMed2002

High-fat diet effects on gut motility, hormone, and appetite responses to duodenal lipid in healthy men.

There is evidence that gastrointestinal function adapts in response to a high-fat (HF) diet. This study investigated the hypothesis that an HF diet modifies the acute effects of duodenal lipid on appetite, antropyloroduodenal pressures, plasma CCK and plasma glucagon-like peptide-1 (GLP-1) levels in humans. Twelve healthy men were studied twice in randomized, crossover fashion. The effects of a 90-min duodenal lipid infusion (6.3 kJ/min) on the above parameters were assessed immediately following 14-day periods on either an HF or a low-fat (LF) diet. After the HF diet, pyloric tonic and phasic pressures were attenuated, and the number of antropyloroduodenal pressure-wave sequences was increased when compared with the LF diet. Plasma CCK and GLP-1 levels did not differ between the two diets. Hunger was greater during the lipid infusion following the HF diet, but there was no difference in food intake. Therefore, exposure to an HF diet for 14 days attenuates the effects of duodenal lipid on antropyloroduodenal pressures and hunger without affecting food intake or plasma hormone levels.

Adult↗
PubMed2002

Laparoscopic renal biopsy in bilateral pelvic kidney with chronic glomerulonephritis.

Percutaneous needle biopsy under the guidance of ultrasound or computerized tomography is the most valuable method in the diagnosis of parenchymal kidney diseases. However, sometimes it can be difficult to perform in the presence of certain anomalies, anatomic variations, or medical problems. In the presence of bilateral pelvic kidney, which is a rare anomaly, laparoscopy can be used to obtain biopsy. Biopsy of kidney was planned in a 26-year-old woman who presented with a history of hypertension for 7 years and proteinuria with the diagnosis of nephrotic syndrome. For the biopsy, the laparoscopic approach was chosen since the patient had bilateral pelvic kidneys. Under general anesthesia, using three port sites, the right kidney was reached, which was located more anterior than the left one. Three biopsy specimens for histologic evaluation were taken with a Tru-Cut biopsy needle. No complications were encountered during or after the operation. The patient was ceased from urological follow-up after performing an ultrasound on the first postoperative day. This is the first case of pelvic kidney with chronic glomerulonephritis reported in the literature in which the histologic diagnosis was made with the help of laparoscopy. Laparoscopic kidney biopsy is a minimally invasive technique that can be done in cases with anatomic variations, making percutaneous needle biopsy impossible.

Adult↗
PubMed2001

Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on antropyloroduodenal motility and appetite in response to intraduodenal lipid infusion in humans.

BACKGROUND: Studies in animals indicate that endogenous nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans. METHODS: On 2 separate days, 8 healthy adult men received intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals. RESULTS: Intraduodenal lipid infusion was associated with increases in fullness (P < 0.05) and in frequency of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05); and decreases in hunger (P < 0.05) and in frequency of antral (P < 0.05) and duodenal (P < 0.05) pressure waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P < 0.05), but had no effect on antropyloroduodenal pressures or food intake. CONCLUSIONS: Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.

Adult↗
PubMed2001

Relationship between ultrasonically detected phasic antral contractions and antral pressure.

The relationships between gastric wall motion and intraluminal pressure are believed to be major determinants of flows within and from the stomach. Gastric antral wall motion and intraluminal pressures were monitored in five healthy subjects by concurrent antropyloroduodenal manometry and transabdominal ultrasound for 60 min after subjects drank 500 ml of clear soup. We found that 99% of antral contractions detected by ultrasound were propagated aborally, and 68% of contractions became lumen occlusive at the site of the ultrasound marker. Of the 203 contractions detected by ultrasound, 53% were associated with pressure events in the manometric reference channel; 86% of contractions had corresponding pressure events detectable somewhere in the antrum. Contractions that occluded the lumen were more likely to be associated with a pressure event in the manometric reference channel (P < 0.01) and to be of greater amplitude (P < 0.01) than non-lumen-occlusive contractions. We conclude that heterogeneous pressure event patterns in the antrum occur despite a stereotyped pattern of contraction propagation seen on ultrasound. Lumen occlusion is more likely to be associated with higher peak antral pressure events.

Adolescent↗
PubMed2000

Radiation dosimetry using polymer gels: methods and applications.

New, complex radiotherapy delivery techniques require dosimeters that are able to measure complex three-dimensional dose distributions accurately and with good spatial resolution. Polymer gel is an emerging new dosimeter being applied to these challenges. The aim of this review is to present a practical overview of polymer gel dosimetry, including gel manufacture, imaging, calibration and application to radiotherapy verification. The dosimeters consist of a gel matrix within which is suspended a solution of acrylic molecules. These molecules polymerize upon exposure to radiation, with the degree of polymerization being proportional to absorbed dose. The polymer distribution can be measured in two or three dimensions using MRI or optical tomography and, after calibration, the images can be converted into radiation dose distributions. Manufacture of the gel is reported to be reproducible, and measured dose in the range 0-10 Gy is accurate to within 3-5%. In-plane image resolution of 1 mm x 1 mm, with image slice thicknesses of between 2-5 mm, is typically achievable using clinical 1.5 T MR scanners and standard T2 weighted imaging sequences. The gels have been used to verify a number of conventional and novel radiotherapy modalities, including brachytherapy, intensity modulated radiotherapy and stereotactic radiosurgery. All the studies have confirmed the value and versatility of the dosimetry technique.

Acrylamide↗
PubMed1999

Validation of a novel luminal flow velocimeter with video fluoroscopy and manometry in the human esophagus.

There is currently no ideal method for concurrently assessing intraluminal pressures and flows in humans with high temporal resolution. We have developed and assessed the performance of a novel fiber-optic laser-Doppler velocimeter, mounted in a multichannel manometric assembly. Velocimeter recordings were compared with concurrent fluoroscopy and manometry following 50 barium swallows in healthy subjects. During these swallows, the velocimeter sensor was situated in either the proximal (24 swallows) or the distal (26 swallows) esophagus. It signaled intraluminal flow following 46 of 50 swallows. A greater mean number of deflections were recorded in the distal compared with the proximal esophagus (4. 3 vs. 2.4, P = 0.001). The maximal flow velocity recorded did not differ between the proximal and distal esophagus (76.7 vs. 73.8 mm/s). No velocimeter signals commenced after fluoroscopic lumen occlusion. The velocimeter signals were closely temporally related to fluoroscopic barium flow. Upward catheter movement on swallowing sometimes appeared to cause a velocimeter signal. Manometrically "normal" swallows were no different from "abnormal" swallows in the number and velocity of deflections recorded by the velocimeter. This novel instrument measures intraluminal flow velocity and pressures concurrently, thus enabling direct study of pressure-flow relationships. Flow patterns differed between the proximal and distal esophagus.

Adult↗
PubMed1998

Spontaneous chronic epidural pneumocephalus resulting from hyperpneumatization of the cranium causing mass effect: case report.

OBJECTIVE AND IMPORTANCE: We report a rare case of spontaneous epidural pneumocephalus resulting from an unusual boney defect caused by hyperpneumatization of the cranium. The pneumocephalus was also unusual for its chronicity and significant mass effect. CLINICAL PRESENTATION: A 49-year-old man presented with a 3-year history of diffuse headaches and sensation of air movement in his sinuses on the right side. An evaluation for suspected sinusitis using computed tomography determined extensive pneumatization of most of the cranium, a large accumulation of epidural air, and a critical degree of brain shift. INTERVENTION: A right frontoparietal-temporal craniotomy with an osteoplastic bone flap was performed. The floor of the middle cranial fossa and the inner table of the bone flap were extensively debrided of air cells. A large pericranial flap was turned down over the floor of the middle cranial fossa and was held in place by a fat graft. After closing the craniotomy, a tympanostomy tube was placed into the right tympanic membrane. CONCLUSION: The incidence of hyperpneumatization of the cranium seems to be very low. Hyperpneumatization when present, however, can cause spontaneous intracranial pneumocephalus. Based on the literature and the success of this case, the optimal management is surgical obliteration of the involved air cells.

Air↗
PubMed1998

Effect of glucose supplementation on appetite and the pyloric motor response to intraduodenal glucose and lipid.

The effects of different macronutrients on appetite and pyloric motility and the impact of short-term dietary glucose supplementation on these responses were evaluated. Ten males (aged 19-38 yr) received isocaloric (2.9 kcal/min) intraduodenal infusions of glucose and lipid while antropyloroduodenal motility and appetite were assessed by manometry and visual analog scales, respectively. Effects of each intraduodenal nutrient on appetite and motility were evaluated before and after 7 days of dietary supplementation with glucose (400 g daily). Initially, both nutrients caused a similar rise in pyloric tone, but intraduodenal lipid was a more potent stimulus of phasic pyloric motility (P = 0.05) and suppressed appetite more (P = 0.013) than intraduodenal glucose. After dietary glucose supplementation, the increase in pyloric tone during intraduodenal glucose was attenuated. Although intraduodenal lipid remained a more potent stimulant of phasic pyloric motility (P = 0.016), it no longer decreased appetite. We conclude that in healthy young males 1) intraduodenal infusion of lipid is a more potent stimulus of phasic pyloric motility and suppresses appetite more than intraduodenal glucose and 2) dietary glucose supplementation alters both the appetite suppressant effect of intraduodenal lipid and the pyloric motor response to intraduodenal glucose infusion.

Adult↗
PubMed1998

Physiological changes in blood glucose affect appetite and pyloric motility during intraduodenal lipid infusion.

We evaluated the effects of varying blood glucose concentration within the normal postprandial range and its interaction with small intestinal nutrients on antropyloric motility and appetite. Eight healthy males (19-40 yr) underwent paired studies, with a blood glucose level of 5 or 8 mmol/l. Manometry and visual analog scales were used to assess motility and appetite, during fasting and intraduodenal lipid infusion (1.5 kcal/min). In the fasting state, antral waves were suppressed at 8 mmol/l compared with 5 mmol/l (P = 0.018). However, pyloric motility was no different between the two blood glucose concentrations. Hunger was no different at 5 mmol/l compared with 8 mmol/l, but fullness was greater at 8 mmol/l (P = 0. 01). During intraduodenal lipid infusion, antral waves were suppressed (P < 0.035) and isolated pyloric pressure waves (IPPWs) were stimulated (P < 0.02) compared with during the fasting state, with no difference between blood glucose concentrations, although the temporal patterning of IPPWs varied between blood glucose concentrations. The amplitude of IPPWs was greater at 5 mmol/l compared with 8 mmol/l (P < 0.001), and hunger decreased at 8 mmol/l compared with 5 mmol/l (P = 0.02). We conclude that "physiological" hyperglycemia modifies gastric motor and sensory function and that synergy exists between blood glucose concentration and small intestinal nutrients in modulating gastric motility and appetite.

Adult↗
PubMed1998

Effects of nitroglycerin on liquid gastric emptying and antropyloroduodenal motility.

The effects of the nitric oxide donor nitroglycerin on gastric emptying and antropyloroduodenal motility were evaluated in nine healthy male subjects (ages 19-36 yr). Antropyloroduodenal pressures were recorded with a manometric assembly that had nine side holes spanning the antrum and proximal duodenum and a pyloric sleeve sensor; gastric emptying was quantified scintigraphically. In each subject, the emptying of 300 ml of 25% glucose labeled with 99mTc was assessed on two separate days during intravenous infusion of either nitroglycerin (5 micrograms/min in 5% dextrose) or 5% dextrose (control). Studies were performed with the subject in the supine position; blood pressure and heart rate were monitored. Nitroglycerin had no significant effect on blood pressure or heart rate. Nitroglycerin slowed gastric emptying (P < 0.02), and this was associated with greater retention of the drink in the proximal stomach (P < 0.05). In both nitroglycerin and control studies, ingestion of the drink was associated with an increase in the number of isolated pyloric pressure waves (P < 0.05) and antral pressure wave sequences (P < 0.05). Nitroglycerin reduced the number of isolated pyloric pressure waves (P < 0.05), basal pyloric pressure (P < 0.05), and the number of antral pressure wave sequences (P < 0. 05), but not the total number of antral pressure waves. The rate of gastric emptying and the number of isolated pyloric pressure waves were inversely related during control (P = 0.03) and nitroglycerin (P < 0.05) infusions. We conclude that in normal subjects, 1) gastric emptying of 300 ml of 25% glucose is inversely related to the frequency of phasic pyloric pressure waves, and 2) nitroglycerin in a dose of 5 micrograms/min inhibits pyloric motility, alters the organization but not the number of antral pressure waves, and slows gastric emptying and intragastric distribution of 25% glucose.

Adult↗
PubMed1998

Effects of meal volume and posture on gastric emptying of solids and appetite.

The effects of volume and posture on gastric emptying and intragastric distribution of a solid meal and appetite were evaluated. Eight normal volunteers were studied on four occasions, on each of which a meal comprising ground beef mixed with tomato sauce of either 650 g ("large") or 217 g ("small") was eaten. Two studies were performed while the subject was lying in the left lateral decubitus position, and two studies were performed while the subject was sitting so that in each subject data were available for both meals and in both postures. Hunger and fullness were evaluated using a visual analog questionnaire. In both postures and after both meals, gastric emptying approximated a linear pattern after an initial lag phase. The lag phase was shorter for the large meal when compared with the small meal [sitting: large 13 +/- 5 vs. small 29 +/- 7 min; left lateral: large 16 +/- 3 vs. small 24 +/- 3 min, F(1, 7) = 46.3, P < 0.0005]. In both postures the contents of the total [F(1,7) = 1794.5, P < 0.0001], proximal [F(1,7) = 203.7, P < 0.0001], and distal [F(1,7) = 231.5, P < 0.0001] stomach were greater after the large meal when compared with the small meal. Although the 50% emptying time was greater with the large than the small meal [F(1,7) = 40.8, P < 0.001], the postlag emptying rate (g/min) was more rapid with the large meal [sitting: large 1.7 +/- 0.2 vs. small 1.1 +/- 0. 1 g/min; left lateral: large 1.8 +/- 0.1 vs. small 1.3 +/- 0.04 g/min, F(1,7) = 44.7, P < 0.0005]. There was a significant interaction between meal volume and posture for retention in the distal stomach [F(1,7) = 7.14, P < 0.05]. Contrasts were used to evaluate the effects of volume and posture between the four studies and demonstrated an effect of posture for the large [F(1,21) = 18.7, P < 0.005] but not the small [F(1,21) = 0.30, P = 0.60] meal so that the retention was greater in the sitting when compared with the left lateral position. The magnitude of the postprandial increase in fullness [F(1,7) = 7.8, P < 0.05] and reduction in hunger [F(1,7) = 5.9, P < 0.05] was greater with the large meal. We conclude that meal volume has a major effect on gastric emptying; in contrast posture has only a minor impact on intragastric meal distribution, which is observed only after a large meal, and no effect on gastric emptying.

Adolescent↗
PubMed1997

Spatial patterns of fasting and fed antropyloric pressure waves in humans.

1. Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with individual gastric contractions. 2. In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum. 3. Pressure wave sequences that occurred during phase II fasting contractions (n = 221) and after food (n = 778) were evaluated. 4. The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade-29% after food and 42% during fasting (P < 0.05); purely synchronous-23% fed and 17% fasting; and purely retrograde-6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences 'skipped' individual recording points. 5. The spatial patterning of gastric pressure wave sequences is diverse, and may explain the differing mechanical outcomes among individual gastric contractions. 6. Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during individual gastric contraction sequences.

Adult↗
PubMed1997

Cancer pathology in the year 2000.

The last one hundred and fifty years has produced the mature and sophisticated discipline of histopathology, yet still leaves the diagnosis of human cancer, by the best available technique, as more art than science. Proton magnetic resonance spectroscopy (1H MRS) ex vivo identifies the chemical markers of established pathobiological disorders within excised biopsies and fine needle aspirates, in particular, those associated with the development and progression of malignant disease. Alterations to cellular chemistry monitored by 1H MRS allows distinction between invasive and pre-invasive lesions of the uterine cervix, and separate truly benign follicular neoplasms from follicular carcinomas on analysis of fine needle aspirates containing as few as 10(6) cells. 1H chemical shift imaging (CSI) determines the spatial location of these chemical changes and provides insight into the chemistry of neoplastic transformation. It is our hypothesis that, by the year 2000, CSI will aid image guided biopsy techniques and that correlation of biopsy histology with in vivo localised 1H MRS data will: (a) lead to improved assessment of the extent of malignant disease and (b) establish the sensitivity and specificity of in vivo 1H MRS for the simultaneous determination of the size, location and neoplastic potential of a tumour mass.

Forecasting↗
PubMed1996

Two-dimensional proton magnetic resonance spectroscopy for tissue characterization of thyroid neoplasms.

We have previously demonstrated that one dimensional (1D) proton (1H) magnetic resonance spectroscopy (MRS) can distinguish normal thyroid tissue from thyroid carcinoma using a spectral ratio of peak intensity at 1.7 ppm/0.9 ppm. Two dimensional (2D) 1H-MRS allows identification of specific molecules that have overlapping peaks in the 1D-MR spectrum. Specimens from 93 consecutive thyroid nodules were examined using 2D 1H-MRS on a Bruker AM-360 wide-bore spectrometer. There was a progressive increase in lipid cross peaks assigned to di-/triglycerides when comparing colloid/hyperplastic nodules to follicular adenoma, and adenoma to carcinoma. A specific cross peak attributable to cholesterol/cholesteryl esters was commonly seen in carcinomas. In contrast, two unassigned cross peaks unique to the thyroid were more prevalent in benign lesions. There was an overall increase in cross peaks attributable to cell surface fucosylation in carcinoma when compared to benign lesions, although the fucose spectral pattern was not specific for cancer. On this basis, a spectral ratio of peak intensity at 2.05 ppm/0.9 ppm more clearly distinguished benign follicular adenoma from carcinoma. 2D 1H-MRS thus identifies chemical changes that allow more specific tissue characterization of thyroid neoplasms.

Adenoma↗
PubMed1996

Effects of glyceryl trinitrate on the pyloric motor response to intraduodenal triglyceride infusion in humans.

The retardation of gastric emptying induced by infusion of triglyceride into the small intestine is associated with suppression of antral pressure waves and stimulation of basal pyloric tone in combination with phasic pressure waves localized to the pylorus. The role of nitric oxide (NO) mechanisms in the control of pyloric motility was evaluated in 12 healthy male subjects (21-43 years), using the NO donor glyceryl trinitrate (GTN). Antropyloric pressures were measured with a manometric assembly incorporating nine sideholes, spanning the antrum and proximal duodenum, and a pyloric sleeve sensor. On separate days, an intraduodenal triglyceride infusion (10% intralipid at 1 mL min-1) was started during antral phase I activity and continued for 60 min. On one of the days GTN (600 micrograms) was given sublingually 20 min after start of the triglyceride infusion. The tonic pyloric motor response to triglyceride [5.6 (SEM 0.8,) vs. 2.7 (1.3) mmHg, P < 0.001] and both the number 3.2 (0.2) vs. 2.2 (0.2) min-1, P < 0.05] and amplitude [40 (4) vs. 27 (5) mmHg, P < 0.05] of phasic isolated pyloric pressure waves were reduced by GTN. These observations suggest that NO mechanisms are involved in the regulation of pyloric motor activity in humans.

Adolescent↗