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D O'Toole

Publications and source records attributed to D O'Toole.

At least 55 records · Page 3Linked to original sources
PubMed2000

Risk factors for diabetes mellitus in chronic pancreatitis.

BACKGROUND & AIMS: The influence of disease progression and pancreatic surgery on the appearance of diabetes mellitus in patients with chronic pancreatitis is unknown. METHODS: A prospective cohort study of 500 consecutive patients with chronic pancreatitis (alcoholics, 85%) followed up over a mean period of 7.0 +/- 6.8 years in a medical-surgical institution between 1973 and 1996 was performed. Multivariate analysis of risk factors for diabetes mellitus was performed after exclusion of 47 patients. Patients who underwent elective pancreatic surgery (n = 231, 51%) were compared with patients who never underwent surgery (n = 222, 49%). RESULTS: The cumulative rate of diabetes mellitus was 83% +/- 4% 25 years after the clinical onset of chronic pancreatitis (insulin requirement, 54% +/- 6%). The prevalence of diabetes mellitus did not increase in the surgical group overall but was higher 5 years after distal pancreatectomy (57% +/- 8%) than after pancreaticoduodenectomy (36% +/- 18%), pancreatic drainage (36% +/- 13%), or cystic, biliary, or digestive drainage (24% +/- 7%) (P = 0. 005), without difference in the latter ones. Pancreatic drainage did not prevent the onset of diabetes mellitus. Distal pancreatectomy (risk ratio, 2.4; 95% confidence interval [CI], 1.6-3.8; P < 0.0001) and early onset of pancreatic calcifications (risk ratio, 3.2; CI, 2. 2-4.7; P < 0.0001) were the only independent risk factors for diabetes mellitus. CONCLUSIONS: The risk of diabetes mellitus is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy in patients with chronic pancreatitis. This risk seems to be largely caused by progression of the disease because it increased by more than 3-fold after the onset of pancreatic calcifications.

Adult↗
PubMed2000

Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses.

AIM: To assess the feasibility and diagnostic accuracy of endoscopic ultrasound guided fine needle biopsy (EUS-FNAB) in patients with solid pancreatic masses. METHODS: Ninety nine consecutive patients with pancreatic masses were studied. Histological findings obtained by EUS-FNAB were compared with the final diagnosis assessed by surgery, biopsy of other tumour site or at postmortem examination, or by using a combination of clinical course, imaging features, and tumour markers. RESULTS: EUS-FNAB was feasible in 90 patients (adenocarcinomas, n = 59; neuroendocrine tumours, n = 15; various neoplasms, n = 6; pancreatitis, n = 10), and analysable material was obtained in 73. Tumour size (>/= or < 25 mm in diameter) did not influence the ability to obtain informative biopsy samples. Diagnostic accuracy was 74.4% (adenocarcinomas, 81.4%; neuroendocrine tumours, 46.7%; other lesions, 75%; p<0.02). Overall, the diagnostic yield in all 99 patients was 68%. Successful biopsies were performed in six patients with portal hypertension. Minor complications (moderate bleeding or pain) occurred in 5% of cases. CONCLUSIONS: EUS-FNAB is a useful and safe method for the investigation of pancreatic masses, with a high feasibility rate even when lesions are small. Overall diagnostic accuracy of EUS-FNAB seems to depend on the tumour type.

Adenocarcinoma↗
PubMed2000

Adaptations in skeletal muscle exercise metabolism to a sustained session of heavy intermittent exercise.

The purpose of this study was to investigate the hypothesis that a single, extended session of heavy exercise would be effective in inducing adaptations in energy metabolism during exercise in the absence of increases in oxidative potential. Ten healthy males [maximal aerobic power (VO(2 peak)) = 43.4 +/- 2.2 (SE) ml x kg(-1) x min(-1)] participated in a 16-h training session involving cycling for 6 min each hour at approximately 90% of maximal oxygen consumption. Measurements of metabolic changes were made on tissue extracted from the vastus lateralis during a two-stage standardized submaximal cycle protocol before (Pre) and 36-48 h after (Post) the training session. At Pre, creatine phosphate (PCr) declined (P < 0.05) by 32% from 0 to 3 min and then remained stable until 20 min of exercise at 60% VO(2 peak) before declining (P < 0.05) by a further 35% during 20 min of exercise at 75% VO(2 peak). Muscle lactate (mmol/kg dry wt) progressively increased (P < 0.05) from 4.59 +/- 0.64 at 0 min to 17.8 +/- 2.7 and 30.9 +/- 5.3 at 3 and 40 min, respectively, whereas muscle glycogen (mmol glucosyl units/kg dry wt) declined (P < 0.05) from a rest value of 360 +/- 24 to 276 +/- 31 and 178 +/- 36 at similar time points. During exercise after the training session, PCr and glycogen were not as depressed (P < 0.05), and increases in muscle lactate were blunted (P < 0.05). All of these changes occurred in the absence of increases in oxidative potential as measured by the maximal activities of citrate synthase and malate dehydrogenase. These findings are consistent with other studies, namely, that muscle metabolic adaptations to regular exercise are an early adaptive event that occurs before increases in oxidative potential.

Adaptation, Physiological↗
PubMed1999

Diagnosis of malignant catarrhal fever by PCR using formalin-fixed, paraffin-embedded tissues.

A previously described polymerase chain reaction (PCR) assay (amplification of a 238-bp fragment of ovine herpesvirus 2 [OHV-2] genomic DNA) for diagnosis of sheep-associated malignant catarrhal fever (MCF) was adapted for use on formalin-fixed, paraffin-embedded tissues. Variables affecting its use were examined. Archived tissues from cattle, white-tailed deer (Odocoileus virginianus), and bison (Bison bison) diagnosed with MCF by clinical signs or histologic lesions were obtained from 2 veterinary diagnostic laboratories. Tissues from healthy animals and from animals diagnosed with other common bovine viral diseases were examined as controls. A total of 86 blocks from 37 suspect MCF cases were examined. Forty-one blocks from healthy animals and animals with unrelated viral diseases were examined as controls. The assay was specific for sheep-associated MCF and did not yield false-positive signals from healthy animals or from cases of infectious bovine rhinotracheitis, bovine virus diarrhea, mucosal disease, or parainfluenza-3 virus infection. A wide variety of tissues were suitable substrates, including spleen, lymph node, intestine, brain, lung, and kidney. Extracted DNA provided a more suitable target than did unextracted tissue lysate. The highest levels of viral DNA were present in lymphoid organs and intestine, but the data indicate that in acute clinical cases, most organs contain sufficient viral DNA to serve as a suitable diagnostic specimen. Fixation of 0.5-cm3 blocks of tissue in 10% neutral buffered formalin was deleterious to the target DNA, and PCR signals progressively diminished after fixation for >45 days. Detection of genomic DNA of OHV-2 by PCR was successful for archived tissues that were 15 years old.

Animals↗
PubMed1998

Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin.

A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentrations (anti-Factor Xa) and clotting times (APTT). Using one of the most effective delivery agents in this series, an estimated relative bioavailability of 8% can be achieved following oral administration to cynomolgus monkeys. To establish a correlation between the in vivo data and an in vitro parameter, immobilized artificial membrane (IAM) chromatography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.

Amino Acids↗
PubMed1998

Transmission of ovine herpesvirus 2 in lambs.

The pattern of acquisition of ovine herpesvirus 2 (OHV-2) infection in lambs was examined by a competitive-inhibition enzyme-linked immunosorbent assay and PCR. Newborn lambs (n = 118) did not exhibit antibody at birth. Viral DNA in peripheral blood leukocytes was detected in only 3% (n = 77) of newborn lambs before suckling. After nursing, viral DNA was sporadically present in about 10 to 20% of lambs until about 3 months of age. Thereafter, strong DNA signals began to appear in increasing numbers of lambs, reaching 100% by 5.5 months of age. Viral DNA in nasal secretions began to be detectable in about 30% of lambs at 5.5 months of age, achieved significant levels in 88% of lambs by 7.5 months of age, and then declined. The kinetics of the humoral immune response in lambs paralleled those of viral DNA in nasal secretions but did not parallel its presence in blood leukocytes. In the experiment to define the time of infection of OHV-2 in lambs, all five lambs separated from the flock at 2.5 months of age remained uninfected until the termination of the experiment at 1 year of age. In contrast, lambs weaned at 2.5 months of age and returned to the flock had become infected at 3.5 months of age. Weaning and separation from the flock at 3.5 months of age did not prevent infection. The study showed that OHV-2 infection does not commonly occur in perinatal lambs and that OHV-2-free sheep can be established by separation of lambs at the proper time, which has important implications for potential control measures.

Animals↗
PubMed1998

H pylori infection is associated with downregulation of E-cadherin, a molecule involved in epithelial cell adhesion and proliferation control.

Extracellular matrix proteins and proteins involved in epithelial adhesion are essential for maintenance of tissue structure. Helicobacter pylori is the major aetiological agent in peptic ulcer disease and has been shown to increase gastric cancer risk up to ninefold. In this study, changes induced by H pylori on the expression of extracellular matrix proteins (collagen IV, fibronectin, and laminin) as well as two essential proteins for cell-basement and cell-cell adhesion (alpha 6-integrin and E-cadherin) were assessed. Immunohistochemistry was performed in antral biopsy sections obtained from infected and non-infected patients, and light microscopy was used to determine the distribution and intensity of specific staining. The results showed that the infection was significantly associated with downregulation of E-cadherin, an essential protein for maintenance of solid tissues and differentiation, but did not induce changes in the expression of alpha 6-integrin or the extracellular matrix proteins.

Cadherins↗
PubMed1997

Chronic and recovered cases of sheep-associated malignant catarrhal fever in cattle.

Malignant catarrhal fever (MCF) is traditionally regarded as a disease with a short clinical course, low morbidity and high case fatality rate. Owing to the limitations of the assays used for laboratory diagnosis. It was difficult in characterise the clinical spectrum of sheep-associated MCF, particularly when the cattle recovered from an MCF-like clinical syndrome. Over a period of three years, 11 cattle that survived MCF for up to two-and-a-half years were identified on four premises. A clinical diagnosis of MCF was confirmed by the detection of ovine herpesvirus-2 DNA in peripheral blood leucocytes using a polymerase chain reaction (PCR) assay that detects a specific 238 base-pair fragment of viral genomic DNA. Of the 11 cattle examined, six recovered clinically with the exception of bilateral corneal oedema with stromal keratitis (four animals) and unilateral perforating keratitis (one animal). The 10 animals available for postmortem examination had disseminated subacute to chronic arteriopathy. Recovery was associated with the resolution of the acute lymphoid panarteritis that characterises the acute phase of MCF, and with the development of generalised chronic obliterative arteriosclerosis. Bilateral leucomata were due in part to the focal destruction of corneal endothelium secondary to acute endothelialitis. Formalin-fixed tissues and/or unfixed lymphoid cells from all 11 cattle were positive for sheep-associated MCF by PCR. These observations indicate that recovery and chronic disease are a significant part of the clinical spectrum of MCF and that such cases occur with some frequency in the area studied. The affected cattle remain persistently infected by the putative sheep-associated MCF gammaherpesvirus.

Animals↗
PubMed1997

Experimentally induced selenosis of adult mallard ducks: clinical signs, lesions, and toxicology.

Selenosis is thought to be a significant problem among waterfowl populations in selenium-contaminated wetlands in the western United States. Chemical analysis of avian tissues is currently the principal basis for diagnosis. The purpose of these two 150-day studies was to establish whether morphological criteria for selenosis could be developed to supplement chemical analysis. Forty-eight flightling male mallard ducks were fed either a proprietary waterfowl ration (< 1 ppm selenium) or the same ration amended to contain 10, 25, and 60 ppm selenium supplied as seleno-L-methionine (n = 12/group). In a separate study, 12 birds fed twice daily were offered either a proprietary ration or a selenium-supplemented ration (120 microg/g) for one of two daily feedings. Selenium in whole blood increased from baseline concentrations (< 0.4 microg/ml) to means of 4.5, 8.9, and 16.0 microg/ml in the 10-, 25-, and 60-ppm groups, respectively. All birds in the 60-ppm-dose group rapidly lost weight and were killed (11/12) or died (1/12) between 22 and 50 days of dietary exposure. In addition to emaciation, six of 12 birds (50%) fed the 60-microg/g diet developed mild to moderate generalized hepatopathy with single-cell necrosis, karyomegaly of hepatocytes, hyperplastic bile duct epithelium, and/or iron accumulation in Kupffer cells. The principal lesions in birds exposed to other dietary concentrations of selenium involved integumentary structures containing hard keratin. Gross lesions developed after 76 days of dietary exposure and consisted of bilaterally symmetrical alopecia of the scalp and dorsal cervical midline, broken or lost digital nails, and necrosis of the tip of the beak (maxillary nail). One or more of these three lesions were present in 0/12 birds (0%) fed 10 ppm selenium, 5/12 birds (42%) fed 25 ppm selenium, and 4/9 (44%) birds fed a split-feed diet containing 120 ppm selenium. Controls were unaffected. Histologic lesions in digital and maxillary nails consisted of single-cell to full-thickness necrosis of keratinocytes and multifocal parakeratosis in stratum corneum. Histologic lesions in alopecic skin (necrosis of the epidermal collar, inflammation of the feather pulp, and follicular keratosis) were mild. Some birds with alopecia had no detectable lesions in feather follicles from affected areas of skin. The highest tissue concentrations of selenium were in liver, kidney, and feathers, respectively. Mean hepatic tissue concentrations were 14.5 microg/g (10 ppm group), 29.6 microg/g (25 ppm group), 60.6 microg/g (60 ppm group), 13.0 microg/g (120 ppm split-feed group), and 2.0 microg/g (controls). Integumentary and hepatic lesions may be of value in corroborating a diagnosis of selenosis based on chemical analysis of tissues from naturally intoxicated waterfowl. Some birds with fatal selenosis may have no morphologic lesions other than emaciation.

Alopecia↗
PubMed1996

Malignant catarrhal fever virus. Characterization of a United States isolate and development of diagnostic assays.

Malignant catarrhal fever (MCF) is a severe lymphoproliferative disease of certain domestic and wild ruminants. Two distinct but closely related viruses cause clinically indistinguishable syndromes in susceptible ruminant species: wildebeest-associated MCF virus (WA-MCFV) and sheep-associated MCF virus (SA-MCFV). Neither the pathogenesis nor the epidemiology of SA-MCF is understood, primarily because of a lack of adequate detection methods for the etiologic agent or antibody against that agent. Work designed to develop these tests has been under way in our laboratory. To obtain basic information about the virus, the in vitro growth properties of a US isolate of MCF virus were studied and its major viral proteins identified and characterized by a panel of monoclonal antibodies generated against the isolate. A monoclonal antibody to a broadly conserved epitope of MCF virus was identified, and a competitive-inhibition ELISA (CI-ELISA) was developed for detection of anti-MCF antibody in sheep and other ruminants. The monoclonal antibody (15-A) reacted with an epitope located on a glycoprotein complex, which was present in all isolates of MCF virus examined. Antibody from a wide variety of ruminants infected with MCF virus of both sheep and wildebeest origin competed with the monoclonal antibody 15-A for the epitope, which was not present on 14 other common ruminant viruses. The assay detected antibody in inapparently infected sheep, and in cattle, deer, and bison with clinical MCF. A PCR assay for DNA of the sheep-associated virus was developed, based on previously reported primers. Comparative studies demonstrated that the CI-ELISA was specific for MCFV antibody and that the PCR was more reliable for diagnosis of clinical MCF.

Animals↗
PubMed1996

4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone.

A series of N-acetylated, non-alpha, aromatic amino acids was prepared and shown to promote the absorption of recombinant human growth hormone (rhGH) from the gastrointestinal tract. Seventy compounds in this family were tested in vivo in rats. Of the compounds tested, 4-[4-[(2-hydroxybenzoyl)amino]phenyl]butyric acid was identified as a preclinical candidate and was used to demonstrate the oral delivery of rhGH in primates. A significant positive correlation was found between the relative log k' of the delivery agents, as determined by HPLC on an immobilized artificial membrane (IAM) column, and serum rhGH concentrations following oral or colonic dosing in rats. Structure-activity relationships have also been developed on the basis of electronic effects and hydrogen-bonding characteristics of the aromatic amide substituents.

Administration, Oral↗
PubMed1996

Insurance-related differences in the presentation of pediatric appendicitis.

In the pediatric population, there is strong evidence to suggest that a delay in treatment results in an increased risk of appendiceal perforation. However, it is not clear whether this delay arises from the parent seeking medical advice, the referring physician seeking surgical consultation, or the surgeon deciding to operate. To resolve this issue, the authors performed a retrospective chart review of all cases of confirmed acute appendicitis that presented to the pediatric surgical service of the Children's Hospital of Buffalo during a 4-year period (January 1990 through December 1993). All children (< or = 16 years of age) were categorized with respect to type of insurance coverage:Medicaid (or uninsured), health maintenance organization (HMO), or private fee-for-service. Their time until emergency room (ER) presentation, operating room (OR) presentation, and hospital discharge were recorded and compared. Their complications and perforation rates also were noted. Two hundred eighty-eight cases were reviewed. The rate of appendiceal perforation was significantly higher among the Medicaid patients (Medicaid, 44%; HMO, 27%; private, 23%; P < .05); their duration of symptoms before presentation was significantly longer (Medicaid, 47.3 +/- 4.1 hours; HMO, 29.3 +/- 1.9 hours; private, 23.1 +/- 2.5 hours; P < .01), and their hospital stay was longer (Medicaid, 7.9 +/- 0.9 days; HMO, 4.8 +/- 0.27 days; private, 4.6 +/- 0.44 days; P < .01). However, there were no significant differences in the time from presentation to the ER until definitive surgery in the OR. Children covered by Medicaid (or uninsured) presented later, had a higher risk of appendiceal perforation, and required a longer hospital stay. The parents of these children either failed to recognize the significance of their children's symptoms, or delayed seeking medical advice because of financial or logistical reasons. The gatekeeper consultation, required by the health maintenance organizations (HMO) did not result in a delay in presentation or have a negative impact on morbidity. Providing easier access to a primary care physician and improving parental health education/awareness may shorten the time until presentation for the uninsured/Medicaid patient.

Acute Disease↗
PubMed1996

Toxicologic evaluation of a high-selenium hay diet in captive pronghorn antelope (Antilocapra americana).

Five captive-raised pronghorn antelope (Antilocapra americana) were fed an alfalfa-grass hay diet containing 15 ppm total dietary selenium (Se) for 164 days. Four additional captive-raised pronghorns fed a similar diet containing approximately 0.3 ppm total dietary Se served as controls. None of the pronghorns had clinical signs attributable to the high Se hay. Plasma Se increased more rapidly than blood Se concentrations, from baseline concentrations (< 0.15 g/ml) to > 0.40 g/ml within the first 50 days on the high selenium diet, but thereafter declined to approximately 0.30 microgram/ml. Mean primary antibody response to hen egg albumin was less in pronghorn on Se hay. No significant gross or histological lesions attributable to selenosis were found, nor was there any evidence of dystrophic hoof growth. The greatest Se tissue concentrations were found in liver and kidney (5.67 to 10.4 micrograms/g and 2.36 to 3.14 micrograms/g, respectively) from experimental animals; liver and kidney from the controls contained considerably less (< or = 0.52 microgram/g and < or = 0.61 microgram/g, respectively). Exposure of pronghorns for more than 5 mo to a diet containing 15 ppm Se caused significant increases in plasma, liver and kidney Se concentrations, in the absence of clinical disease or pathologic lesions due to selenosis. Based on these results, we propose that pronghorns are less susceptible to selenosis than previously reported and that diagnostic criteria for the disease should be modified.

Animals↗
PubMed1996

Prevalence of antibody to malignant catarrhal fever virus in wild and domestic ruminants by competitive-inhibition ELISA.

A competitive-inhibition ELISA (CI-ELISA), based on a monoclonal antibody to an epitope conserved among malignant catarrhal fever virus (MCFV) strains of both wildebeest and sheep origin, was used to determine the prevalence of antibody to MCFV in selected domestic and wild ruminants, both free-ranging and captive, from the USA. We evaluated 2528 sera from 14 species between 1990 and 1995, including 80 pronghorn antelope (Antilocapra americana), 339 bighorn sheep (Ovis canadensis), 103 biston (Bison bison), 17 black-tailed deer (Odocoileus hemionus columbianus), 395 domestic cattle (Bos taurus), 291 domestic goats (Capra hircus), 680 domestic sheep (Ovis ammon), 323 elk (Cervus elaphus), 41 llamas (Lama glama), 21 mouflon sheep (Ovis musimon), 54 mountain goats (Oreamnos americanus), 101 mule deer (Odocoileus hemionus), 20 muskox (Ovibos moschatus), and 63 white-tailed deer (Odocoileus virginianus). A high seroprevalence (37 to 62%) was observed in domestic sheep, domestic goats, muskox, and some bighorn sheep populations. Seroprevalence in these species was generally age-related: a very low seroprevalence was present in these animals under one year of age. A low seroprevalence (2% to 13%) was found in clinically-susceptible species such as domestic cattle, deer, elk and bison, supporting the concept that significant numbers of non-lethal infections occur among clinically susceptible ruminants.

Age Factors↗
PubMed1995

Myositis, lameness, and paraparesis associated with use of an oil-adjuvant bacterin in beef cows.

Right hind limb lameness, progressing to bilateral paraparesis, was observed in 56 of 610 (9%) beef cows. Lameness began 6 days to 4 weeks after vaccination in the right longissimus lumborum (loin) muscle with an Escherichia coli/Campylobacter bacterin in an oil adjuvant. Postmortem examination of 5 affected cows revealed a large inflammatory mass at the site of vaccination. In each cow, the mass spread through adjacent intervertebral foramina into the vertebral canal and compressed the lumbar portion of the spinal cord. Microbiologic procedures did not reveal a microbial agent in affected tissues or in an unopened bottle of bacterin from the same lot used in the herd. Histologic examination revealed pyogranulomatous inflammation of the vaccination site and adjacent epidural tissue, with inflammatory nodules centered around large clear spaces that probably represented remnant emulsion from the oil adjuvant in the bacterin. As evident in these cows, IM injection of irritating products may cause severe myositis. Vaccination into paravertebral muscles is risky because of possible extension of inflammation through intervertebral foramina.

Adjuvants, Immunologic↗