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D O'Toole

Publications and source records attributed to D O'Toole.

At least 37 records · Page 2Linked to original sources
PubMed2002

Increases in muscle MCT are associated with reductions in muscle lactate after a single exercise session in humans.

To investigate the effects of a single session of prolonged cycle exercise [60% peak O2 uptake (VO2 peak) for 5-6 h] on metabolic adaptations in working vastus lateralis muscle, nine untrained males (peak O2 uptake = 47.2 +/- 1.1 ml x kg(-1) x min(-1), means +/- SE) were examined before (Pre) and at 2 (Post-2), 4 (Post-4), and 6 (Post-6) days after the training session. On the basis of 15 min of cycle exercise at 59% VO2 peak, it was found that training reduced (P < 0.05) exercise muscle lactate (mM) at Post-2 (6.65 +/- 0.69), Post-4 (7.74 +/- 0.63), and Post-6 (7.78 +/- 1.2) compared with Pre (10.9 +/- 1.3). No effect of training was observed on exercise ATP, phosphocreatine, and glycogen levels. After the single session of training, plasma volumes were elevated (P < 0.05) at Post-2 (6.7 +/- 1.7%), Post-4 (5.86 +/- 1.9), and Post-6 (5.13 +/- 2.5). The single exercise session also resulted in elevations (P < 0.05) in the monocarboxylate transporters MCT1 and MCT4 throughout the 6 days after exercise. Although epinephrine and norepinephrine both increased with exercise, only norepinephrine was reduced (P < 0.05) with training and only at Post-4. These results indicate that regulation of cellular lactate levels occurs rapidly and independently of other metabolic adaptations. It is proposed that increases in MCT and plasma volume are at least partly involved in the lower muscle lactate content observed after the training session by increasing lactate membrane transport and removal, respectively.

Adult↗
PubMed2002

Malignant catarrhal fever in a bison (Bison bison) feedlot, 1993-2000.

A fatal enteric syndrome was identified in American bison (Bison bison) at a large feedlot in the American Midwest in early 1998. An estimated 150 bison died of the syndrome between January 1998 and December 1999. The syndrome was identified as malignant catarrhal fever (MCF), primarily the alimentary form. Clinical onset was acute, and most affected bison died within 1-3 days; none recovered. Consistent lesions were hemorrhagic cystitis, ulcerative enterotyphlocolitis, and arteritis-phlebitis. Vasculitis was milder and more localized than that in cattle with MCF, and in contrast to the situation in cattle, lymphadenomegaly was minimal. Virtually all affected bison examined were positive for ovine herpesvirus 2 (OvHV-2) by polymerase chain reaction (PCR) assay. A retrospective study of archived tissues established that MCF occurred in the yard as early as 1993. A prospective study was undertaken to establish the importance of MCF relative to other fatal diseases at the feedlot. The fate of a group of 300 healthy male bison in a consignment of 1,101 animals was followed for up to 7 months to slaughter. At entry, 23% (71/300) of bison were seropositive for MCF viruses, and 11% (8/71) of these seropositive bison were PCR positive for OvHV-2. Forty seronegative bison were selected at random from the group, and all were PCR negative for OvHV-2. There was no change in seroprevalence in the group during the investigation. The minimum infection rate for MCF virus was 36.3% (93/256). Twenty-two (7.3%) of the 300 bison in the feedlot died. Of these, 15 had MCF, 4 had acute or chronic pneumonia, and 3 were unexamined. Losses in the entire consignment were higher (98/1,101; 8.8% death loss); 76% of deaths were attributable to MCF. The study failed to reveal a relationship between subclinical infection and development of clinical disease.

Animals↗
PubMed2002

Interferon-beta-1b and interferon-gamma have similar inhibitory effects on apolipoprotein-E production in the monocyte/macrophage.

Apolipoprotein-E (Apo-E) is the major lipid carrier in the brain, and is therefore important in the recyding of lipids and cholesterol to regenerating neurons during the remission phase of multiple sclerosis (MS). Interferon (IFN)-gamma has been shown to inhibit Apo-E production by a mainly post-transcriptional method in a macrophage cell line, and reduced Apo-E in cerebrospinal fluid is noted during the remission phase in patients. IFN-beta-1b is a recombinantly produced, anti-inflammatory cytokine, which has been shown to reduce the severity of MS relapses and reduce relapse rate. We have examined the effects of IFN-gamma and IFN-beta-1b on the production of Apo-E mRNA, cellular protein and secreted protein in primary monocytes derived from donor blood. IFN-beta-1b does not relieve the dose-dependent inhibition of Apo-E seen with IFN-gamma at up to 100 U/ml in these cells, and when used alone inhibits Apo-E production in a dose-dependent manner. This inhibition by IFN-beta-1b was seen to be at a transcriptional level, and dose dependent up to 100 U/ml. Apo-E genotype, which has also been linked to failure to recover from MS relapses, did not affect this inhibition. The mode of action of IFN-beta-1b in MS is therefore not thought to be through modification of Apo-E production.

Apolipoproteins E↗
PubMed2001

Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct.

BACKGROUND: Chronic obstruction of the common bile duct may cause hepatic fibrosis and secondary biliary cirrhosis. METHODS: We studied liver-biopsy specimens from 11 patients with chronic stenosis of the common bile duct due to chronic pancreatitis; all the patients had undergone liver biopsy before or at the time of surgical biliary decompression and underwent a subsequent liver biopsy for various clinical reasons. The patients were followed as part of a prospective study of 501 patients who had been treated for chronic pancreatitis. Two pathologists, who were unaware of the sequence of specimens, graded fibrosis on a scale of 0 (none) to 3 (cirrhosis). RESULTS: The 11 patients were all men. Chronic pancreatitis was due to alcohol abuse in 10 of the men; 1 had idiopathic disease. The median age at diagnosis was 38 years. The median interval between the first and second liver biopsies was 2.5 years (range, 0.3 to 9.0). The two patients who had restenosis of the biliary anastomosis were excluded from the analysis of fibrosis. In the group of nine patients without restenosis, the second specimen showed significant improvement in fibrosis (P=0.01). The fibrosis improved by two grades in two patients and by one grade in four patients; in three patients, the grade did not change. The pathologists agreed on the grading of specimens from 10 of the 11 patients. CONCLUSIONS: In patients with chronic pancreatitis and stenosis of the common bile duct, liver fibrosis may regress after biliary drainage.

Adult↗
PubMed2001

Incidence and reversibility of organ failure in the course of sterile or infected necrotizing pancreatitis.

BACKGROUND: Multiple organ failure (MOF) and infected necrosis are both considered severe adverse events during the course of necrotizing pancreatitis. HYPOTHESIS: The incidence of MOF and its reversibility in patients with necrotizing pancreatitis are influenced by the presence or absence of infected necrosis. DESIGN: Case series. SETTING: Intensive care, university teaching hospital. PATIENTS: Forty-three patients with necrotizing pancreatitis and failure of at least 1 organ were prospectively included. MAIN OUTCOME MEASURES: Organ failure defined according to the Goris classification; MOF defined by the simultaneous occurrence of 3 organ failures and graded with an MOF score. Microbial status of necrosis was assessed by percutaneous or intraoperative sampling. Surgical drainage was performed in patients with infected necrosis, whereas sterile necrosis was managed conservatively. RESULTS: Infected necrosis occurred in 27 patients (63%). The mean (+/-SEM) number of organ failures was greater in cases of infection (3.6 +/- 1.1 vs 2.6 +/- 1.5; P =.02). Multiple organ failure occurred more frequently in cases of infected necrosis (23/27 vs 7/16; P<.01) and was responsible for an increased mortality in this subgroup (33% vs 6%; P =.1). The severity of MOF graded by the MOF score was related to the bacteriologic status of necrosis. CONCLUSIONS: The higher mortality commonly attributed to MOF in patients with infected necrosis appears to be due to a higher frequency and an increased severity of MOF. Conservative management in patients with severe necrotizing pancreatitis and sterile necrosis complicated by MOF is supported by the high reversibility rate of MOF and the low mortality rate observed in this series.

APACHE↗
PubMed2001

Immediate and short-term cellular and biochemical responses to pulmonary single-dose studies of insulin and H-MAP.

PURPOSE: It was previously reported that co-administration of H-MAP to the airways of the lungs significantly influenced the absorption, disposition. and effect of insulin in a dose-dependent fashion. Doses of H-MAP (16 mg/kg) and insulin (1.3 U/kg) required to achieve maximum pharmacokinetic and pharmacodynamic responses were determined. The purpose of the present study was to evaluate the effects of insulin and H-MAP spray-instilled (SI) to rats on the physiology of the lung. A short-term, single-dose study of insulin alone and combined with H-MAP was performed. METHODS: Solutions of either insulin (INS), H-MAP, or insulin plus H-MAP (INMA) were SI to the lungs of rats. Lipopolysaccharide solution (LPS) and sodium dodecyl sulfate solution (SDS) were used as positive controls. and normal saline (SAL) was used as negative control. Animals were sacrificed at various time points and bronchoalveolar lavage (BAL) was conducted. BAL fluid was analyzed for local markers of lung injury, such as total cell numbers, differential cell count, total protein content and enzyme activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and N-acetyl glucosaminidase (NAG). RESULTS: SI of any solution, including normal saline, seems to have a minor but detectable effect on the normal physiology of the lung. SI of positive control solutions resulted in most markers of immunity and lung injury being significantly elevated, notably enzyme activity and white cell infiltrate. In contrast, SI of INS produced a response similar to that of SAL. SI of INMA resulted in a small transient response characterized by a slight increase in the proportion of neutrophils at 24 h, which decreased with time and was comparable to that of SAL at 72

Alkaline Phosphatase↗
PubMed2001

Facilitation of pulmonary insulin absorption by H-MAP: pharmacokinetics and pharmacodynamics in rats.

PURPOSE: Several low molecular weight amino acids have previously been reported to enable the oral delivery of proteins. In the present studies, the effect of H-MAP (hydroxy methyl amino propionic acid) on the pharmacokinetics (PK) and pharmacodynamics (PD) of porcine insulin delivered to the lungs of rats by spray-instillation (SI) has been determined. METHODS: Aliquots (100 microl) of increasing doses of porcine insulin alone (0.26, 1.3, 2.6, 13, and 26 U/kg) or combined with increasing doses of H-MAP (5, 10, 16, and 25 mg/kg), at pH 7.2-7.6 were administered intratracheally to fasted anesthetized rats using a micro spray-instillator. Blood samples were collected from the jugular vein at specified intervals and the plasma concentrations of insulin and glucose were determined. The PK and PD of porcine insulin alone following subcutaneous (SC) administration of increasing doses were also determined. RESULTS: The PK of insulin administered either by SI to the lungs or SC injection were absorption rate dependent, resulting in post-peak half-lives 10 to 25-fold greater than the reported intravenous elimination half-life (3 min). The relative bioavailability (F') of insulin administered alone by SI varied from 23.8 to 80% for the lowest and highest insulin dose, respectively. Co-administration of H-MAP and insulin to the lungs significantly changed the PK and PD of insulin in a dose dependent fashion. Maximum PK and PD responses were obtained at an H-MAP dose of 16 mg/kg and an insulin dose of 1.3 U/kg. At this combination, the relative bioavailability of insulin was increased more than 2.5 fold, maximum concentration (Cmax) increased 2-fold and the minimum plasma glucose concentration (%MPGC) was reduced more than 2-fold with respect to same dose of insulin alone. A greater total reduction in plasma glucose (%TRPG0-->t) was achieved for H-MAP/insulin combination (66+/-5%) compared to insulin alone (47+/-10 %). CONCLUSION: H-MAP has potential for increasing the pulmonary bioavailability of insulin administered through the lungs.

Absorption↗
PubMed2001

Assessment of complications of EUS-guided fine-needle aspiration.

BACKGROUND: EUS-guided fine-needle aspiration (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Despite increasing use of this technique, the safety and overall complication rates remain poorly defined. METHODS: During a period of 20 months, 322 consecutive patients underwent EUS-FNA in 2 centers. All procedures were performed with the patients under general anesthesia. All complications (including local complications resulting from endoscopy/aspiration or clinical complications after the procedure) were evaluated. Potential risk factors for the development of complications were also analyzed including site and nature of the lesion, presence of portal hypertension, and number of needle passes. RESULTS: A total of 345 lesions were aspirated in 322 patients. EUS-FNA involved the pancreas in 248 cases. Pancreatic lesions included solid (134) and cystic (114) types, which required a mean of 2.5 and 1.4 needle passes, respectively. Complications were observed in 4 (1.2%) patients after aspiration of pancreatic cystic lesions (acute pancreatitis, n = 3; aspiration pneumonia, n = 1) and all cases of pancreatitis resulted from FNA of lesions in the head/uncinate process. No complications resulted from FNA of solid pancreatic lesions. Complications were not observed after FNA of lymph nodes (n = 62) and one case of aspiration pneumonia was observed after FNA of a stromal tumor. EUS-FNA was performed without complication in 16 patients (5%) with portal hypertension. The number of needle passes was not predictive of complications. CONCLUSIONS: Because the overall risk of complications from EUS-FNA was relatively low (1.6%) with no severe or fatal incidents and although the risk appears slightly higher than that for standard EUS alone, the safety of EUS-FNA appears acceptable based on this analysis from an experienced center.

Biopsy, Needle↗
PubMed2001

Hepatic failure and hemochromatosis of Salers and Salers-cross cattle.

Hemochromatosis is rare in domestic mammals. Five clinical cases and one preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross cattle. Clinical disease developed between 9 and 22 months of age. Animals were healthy until weaning but then lost weight, developed rough hair coats, and lost incisor teeth. In two animals, hemochromatosis was identified by liver biopsy, biochemical evidence of hepatic injury, and/or elevated transferrin saturation values. At necropsy, carcasses were thin, with firm dark brown livers and lymph nodes, soft bones, and brown-colored small bowel. The principal histologic changes were hepatocellular siderosis and periportal, bridging, and perivenular fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic iron concentrations in clinically affected cattle were 1,500-10,500 microg/g wet weight (reference range for cattle = <300 microg/ g). Ultrastructurally, the heaviest intrahepatic deposition was in hepatocytes, which contained large intracytoplasmic siderosomes. Iron deposition in bone was associated with osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees of five of six affected cattle; no pedigree was available for the remaining animal. Four dams of five affected animals were phenotypically normal and had histologically normal livers. Test mating of four cows to the ancestral bull resulted in a female calf that developed clinicopathologic and histologic evidence of preclinical hemochromatosis by 40 days of age. It was not possible to establish the pattern of inheritance because of the small number of pedigrees from affected cattle.

Animals↗
PubMed2000

Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay.

Heparin is the anticoagulant of choice for hospitalized patients, but it is dosed only by injection because it is not absorbed following oral administration. We have discovered and prepared compounds (delivery agents) that facilitate the gastrointestinal absorption of heparin in rats, monkeys, and humans when given orally. We are currently developing a parallel synthesis approach to increase our delivery agent screening throughput in vivo. This approach has been used to produce micromolar quantities of compounds for testing in rats in a 5 x 5 parallel synthesis array. Using an amine benzoylation reaction sequence, 10 mixtures were prepared. These mixtures contained equal weight quantities of five N-substituted, non-alpha, amino acid delivery agents. Each of these mixtures was orally administered to rats in combination with heparin, and plasma clotting times (APTT) were measured to determine activity. Deconvolution of the data accurately identified the most active individual components. Independent synthesis of these compounds verified their activity. This parallel synthesis approach is an effective tool for the screening of oral heparin delivery agents and has increased screening throughput significantly.

Amino Acids↗
PubMed2000

Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance.

BACKGROUND: The somatostatin analogues lanreotide and octreotide have previously been shown to be effective in controlling flushing and diarrhea in patients with carcinoid syndrome. As lanreotide requires injection only every 10 days, compared with twice-daily injections of octreotide, a direct comparison between these two treatments in terms of patient acceptability, patient preference, and efficacy in controlling symptoms was performed in patients with carcinoid syndrome. METHODS: Thirty-three patients with carcinoid syndrome were included in an open, multicenter, crossover study. Half of the patients received octreotide 200 microg subcutaneously twice or thrice daily for 1 month followed by lanreotide 30 mg intramuscularly every 10 days for 1 month, while the other half commenced with lanreotide followed by octreotide in a similar fashion. Quality-of-life assessments were performed at each visit and patient preference for one of the two treatments evaluated. The number and intensity of flushing episodes and bowel movements, urinary 5-hydroxyindoleacetic acid (5HIAA) levels, and plasma serotonin levels were recorded. RESULTS: No significant differences were found between lanreotide and octreotide in terms of quality of life. The majority of patients (68%) preferred lanreotide (P = 0.03), largely due to its simplified mode of administration. Disappearance or improvement in flushes occurred in 53.8% of patients (14 of 26) while on lanreotide and in 68% (17 of 25) on octreotide. A disappearance or improvement of diarrhea in 45.4% (10 of 22) on lanreotide, compared with 50% (11 of 22) on octreotide, was also observed. Lanreotide and octreotide were equally effective in reducing urinary 5HIAA levels and plasma serotonin levels. Both treatments were well tolerated, with mild symptoms of abdominal pain and nausea observed in 29% and 14% receiving octreotide and lanreotide, respectively. CONCLUSIONS: Lanreotide and octreotide are equally efficacious in terms of symptom control and reduction in tumor cell markers for patients with carcinoid syndrome. Due to its simplified mode of administration, most patients prefer treatment with lanreotide.

Antineoplastic Agents↗
PubMed2000

Intrahepatic hemodynamic changes following portal vein embolization: a prospective Doppler study.

The aim of this study was to describe the intrahepatic hemodynamic modifications induced by right portal vein embolization (RPVE) using Doppler ultrasound. Eighteen patients with hepatocellular carcinoma (n = 8), liver metastases (n = 9), or multiple adenomas, underwent RPVE 1 month before right hepatectomy in order to increase the size of future remnant liver. Doppler ultrasound was performed before and 1 month after RPVE. The portal vein flow and the hepatic artery resistive index in right and left lobes (segments V and III) were calculated. We recorded simultaneously artery and portal vein of segment III to measure the arterioportal ratio calculated as follows: (maximal arterial systolic velocity minus maximal portal vein velocity)/maximal arterial systolic velocity. Results were compared in cirrhotic patients (group A) and in healthy liver patients (group B). In both groups, portal flow was not significantly modified following RPVE. In the left lobe, in both groups the hepatic artery resistive index was not significantly modified. In group B, the arterioportal ratio decreased significantly (0.71 +/- 0.18 and 0.42 +/- 0.23, respectively, before and after embolization; p < 0.01), whereas it was not statistically modified in group A (0.75 +/- 0.17 and 0.69 +/- 0.14, respectively, before and after embolization). The right hepatic arterial resistive index decreased significantly in both groups after embolization (0.74 +/- 0.07 to 0.66 +/- 0.07, p<0.05; and 0.66 +/- 0.07 to 0.61 +/- 0.06, p < 0.05, respectively, before and after RPVE for groups A and B). Total portal flow was unchanged after RPVE (750 +/- 337 ml/mn and 696 +/- 231 ml/mn, respectively, before and after RPVE). The hepatic artery resistive index was unchanged before and after embolization in the left lobe (0.75 +/- 0.13 and 0.74 +/- 0.14, respectively), but significantly decreased in the right lobe (0.7 +/- 0.08 and 0.62 +/- 0.06 respectively, p < 0.05). The left arterioportal ratio decreased significantly from 0.76 +/- 0.17 to 0.52 +/- 0.23 after PVE, p < 0.02). Our study confirms that right portal occlusion induces a decrease in hepatic artery resistive index in the right lobe and does not modify total portal flow. The left and right lobes of the liver have separate arterioportal regulation.

Carcinoma, Hepatocellular↗
PubMed2000

High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.

BACKGROUND & AIMS: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. METHODS: Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. RESULTS: Compared with controls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/- 2.8 vs. 11.9 +/- 1.0; P <0.0001) and patients with ulcerative colitis who required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11.9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). CONCLUSIONS: PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Transmission of ovine herpesvirus 2 among adult sheep.

Previous studies from this laboratory have defined the pattern of acquisition of ovine herpesvirus 2 (OHV-2) in lambs under natural flock conditions. This study examined the question of whether OHV-2 could be transmitted between adult sheep. Two potential routes of transmission were examined: (1) direct inoculation of either viable leukocytes or whole blood from OHV-2 positive sheep, and (2) horizontal transmission through natural contact with OHV-2 positive sheep. Two groups of OHV-2 negative adult sheep were inoculated with material from infected sheep, one with 5x10(8) viable peripheral blood leukocytes (PBL), and the other with 100 ml of whole peripheral blood. No PCR signals were detected in any of the three sheep inoculated with the PBL during the 20 weeks following inoculation. In the group of five sheep inoculated with whole blood, two became PCR-positive at 7 and 8 weeks post-inoculation, respectively, and the remaining three sheep maintained their negative status until termination of the experiment at 20 weeks post-inoculation. In two experiments conducted in different flocks, a total of 20 adult sheep were used to examine horizontal transmission by contact; all animals became PCR-positive within 12 months of mixing the uninfected and infected animals. The results of these experiments support two conclusions. First, the susceptibility to OHV-2 is not limited to young lambs; adult sheep remain fully susceptible. Second, the fact that whole blood, but not PBL, from infected sheep was able to transmit the infection to only two of five inoculated sheep suggests that the infection in peripheral blood cells may be largely non-productive.

Animals↗
PubMed2000

Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line.

Activated protein C (APC) protects against sepsis in animal models and inhibits the lipopolysacharide (LPS)-induced elaboration of proinflammatory cytokines from monocytes. The molecular mechanism responsible for this property is unknown. We assessed the effect of APC on LPS-induced tumour necrosis factor alpha (TNF-alpha) production and on the activation of the central proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in a THP-1 cell line. Cells were preincubated with varying concentrations of APC (200 microg/ml, 100 microg/ml and 20 microg/ml) before addition of LPS (100 ng/ml and 10 microg/ml). APC inhibited LPS-induced production of TNF-alpha both in the presence and absence of fetal calf serum (FCS), although the effect was less marked with 10% FCS. APC also inhibited LPS-induced activation of NF-kappaB, with APC (200 microg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to inhibit LPS-induced translocation of NF-kappaB is likely to be a significant event given the critical role of the latter in the host inflammatory response.

Analysis of Variance↗
PubMed2000

Functional and morphological changes in the pancreatic remnant following pancreaticoduodenectomy with pancreaticogastric anastomosis.

BACKGROUND: The aim was to evaluate pancreatic exocrine and endocrine function, pancreatic atrophy and main pancreatic duct dilatation in the pancreatic remnant following pancreaticoduodenectomy and pancreaticogastrostomy. METHODS: Nineteen patients who underwent pancreaticoduodenectomy and pancreaticogastrostomy for benign or malignant pancreatic tumours with a histologically normal pancreatic resection margin were studied prospectively. The median interval between operation and evaluation was 32 (range 12-120) months. Pancreatic exocrine insufficiency was assessed by measuring 72-h faecal fat concentrations and faecal-1 elastase. Fasting blood glucose, haemoglobin A1c, serum peptide C and insulin levels were used to assess endocrine function. Pancreatic parenchymal thickness and main pancreatic duct diameter were measured before operation and at evaluation using computed tomography (CT). RESULTS: Faecal fat excretion was raised in 16 of 17 patients; faecal-1 elastase was reduced in all 17 patients. None of the 17 non-diabetic patients had developed diabetes mellitus at follow-up. A significant decrease in pancreatic parenchymal thickness and increased dilatation of the main pancreatic duct were observed on CT at evaluation (P = 0.01 and P = 0.01 respectively). Pancreatic atrophy, assessed by subtracting the diameter of the pancreatic duct from the total gland thickness, tended to develop over time, but at the limit of statistical significance (P = 0.06). CONCLUSION: A median of 3 years following pancreaticoduodenectomy and pancreaticogastrostomy, patients remained free from diabetes but developed marked pancreatic exocrine insufficiency. Presented in part to the Societé Nationale Française de Gastroentérologie in Nantes, March 1999, and published in abstract form as Gastroenterol Clin Biol 1999; 23: A81

Adult↗
PubMed2000

Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d'Etude de la Maladie de von Hippel-Lindau.

BACKGROUND & AIMS: Pancreatic involvement in von Hippel-Lindau (VHL) disease, a genetic disorder with a dominant mode of inheritance affecting various organs, has rarely been studied. We assessed the prevalence, type of lesions, natural history, and impact of pancreatic involvement in patients with VHL. METHODS: A total of 158 consecutive patients from 94 families with VHL disease were studied in a prospective French collaborative study. All patients underwent systematic screening for VHL lesions, including computerized tomography (CT) scanning of the pancreas reviewed by an experienced radiologist. Clinical data, investigations, and treatments performed were also reviewed. RESULTS: Pancreatic involvement was observed in 122 patients (77.2%) and included true cysts (91.1%), serous cystadenomas (12.3%), neuroendocrine tumors (12.3%), or combined lesions (11.5%). The pancreas was the only organ affected in 7.6% of patients. Patients with pancreatic lesions had fewer pheochromocytomas than those without (14/122 vs. 16/36; P<0.0001), and patients with neuroendocrine pancreatic tumors had renal involvement less often than those without (8/99 vs. 6/20; P = 0.013). None of the patients with neuroendocrine tumors had symptoms of hormonal hypersecretion. Pancreatic lesions evolved in half of patients but required specific treatment in only 10 (8.2%) when they were symptomatic or for the resection of large neuroendocrine tumors. CONCLUSIONS: Pancreatic involvement is seen in most patients with VHL disease. Although symptoms are rare, specific treatment of pancreatic lesions is required in selected patients, mainly those with neuroendocrine tumors.

Adult↗