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Biomedical subjects

J F Fitzgerald

Publications and source records attributed to J F Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1999

A comparison of the effect of three sedatives on esophageal sphincters in cats.

BACKGROUND/AIMS: Children 5 years old and younger often require sedation for esophageal motility studies (EMS). At our institution, an intramuscular cocktail of meperidine, promethazine and chlorpromazine (MPC) has been used as the standard sedative for young children undergoing EMS. Administering the intramuscular sedative may, however, be more traumatic to the child than the procedure. Moreover, its effect on esophageal motility is not known and prolonged sedation is common. The aim of this study was to determine the effects of MPC and two orally-administered sedatives on esophageal sphincter function, using the cat model, with a goal to identify a potentially suitable orally-administered sedative for use in young children requiring sedation for EMS. METHODS: We measured upper (UESP) and lower (LESP) esophageal sphincter pressures in 25 cats initially without sedation, and then following sedation with midazolam, chloral hydrate and MPC. The results were compared. RESULTS: All three sedatives significantly decreased LESP compared to the control (p<0.05). Midazolam decreased LESP the most; however, the difference from the other sedatives did not reach statistical significance. All three sedatives decreased UESP, compared to control, but the differences were not statistically significant. Of the two oral sedatives, chloral hydrate had the least effect on the esophageal sphincters although its effect was not statistically different from that of midazolam. CONCLUSIONS: Ethically appropriate studies are needed to determine which oral sedative would be most beneficial for use in sedating children undergoing esophageal motility studies. Until studies can be done, the choice between chloral hydrate and midazolam should be based on the experience and comfort of the attending physician with regard to the potential side effects of the medications.

Analgesics, Opioid↗
PubMed1999

Tyrosinemia type 1 should be suspected in infants with severe coagulopathy even in the absence of other signs of liver failure.

Tyrosinemia type l is an inherited metabolic disorder attributable to deficiency of fumarylacetoacetate hydrolase, a terminal enzyme in the degradation pathway of tyrosine. Affected individuals may present with any of a number of signs and symptoms, including failure to thrive, fever, vomiting, diarrhea, hepatomegaly, ascites, jaundice, renal Fanconi syndrome, or conditions such as rickets and hepatocellular carcinoma.1 If untreated, the patient may die of acute liver failure before the second year of life, or from chronic liver failure or hepatocellular carcinoma before the end of the second decade of life.2 Although overt liver failure with coagulopathy may be part of the presentation of tyrosinemia, a significant coagulopathy in the absence of overt signs of liver disease has not been emphasized as a clue to the diagnosis of this condition. We report two tyrosinemic infants who presented with severe coagulopathies and no other signs of liver failure to stress this diagnostic point.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Further studies of anti-endomysium and anti-gliadin antibodies in patients with suspected celiac disease.

BACKGROUND: The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health-care costs. The sensitivity and specificity of anti-gliadin antibodies (AGA-immunoglobulin [Ig] G, AGA-IgA) have been variable; anti-endomysium IgA (EmA-IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti-endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA-IgA in diagnosing celiac disease. METHODS: One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA-IgA was measured in all patients, and AGA-IgG and AGA-IgA were measured in 104 patients. Forty-six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients. RESULTS: Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2-9.5 years); one also had cystic fibrosis and another had insulin-dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA-IgA (100% sensitivity). None of the remaining patients had increased EmA-IgA (100% specificity). Serum levels of AGA-IgG and AGA-IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of the alpha-glucosidases (n = 1). CONCLUSIONS: This study confirmed the reliability and accuracy of EmA-IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA-positive patients in whom celiac disease is suspected.

Antibodies↗
PubMed1998

Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population.

OBJECTIVE: Increasing evidence suggests that nitric oxide participates in the pathophysiology of intestinal barrier function/dysfunction and inflammation. Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression have been observed in colonic mucosal biopsies of adults with inflammatory bowel disease (IBD). It is unclear whether iNOS induction is specific for IBD or a reflection of nonspecific mucosal inflammation. Furthermore, the characteristics of iNOS mRNA expression in pediatric patients with gastrointestinal disorders remains ill-defined. Our objective was to examine the relationship between iNOS mRNA expression and gastrointestinal mucosal inflammation in a pediatric population. METHODS: Esophageal and colonic mucosal biopsies were obtained during endoscopy. Total RNA was isolated from these biopsies and reverse transcription-polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp primers that amplified a predicted 372-bp conserved iNOS mRNA fragment. RESULTS: Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7-16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR amplification in six of 10 patients with ulcerative colitis and in two of four patients with Crohn disease. However, iNOS mRNA was not amplified in any esophageal biopsy or in rectal mucosa biopsies with normal histology. CONCLUSIONS: These data indicate that upregulation of iNOS mRNA expression in colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not upregulated in esophageal mucosa or in the absence of colonic inflammation. Further studies designed to determine the site- and cell-specificity of iNOS mRNA upregulation in mucosal biopsies from children with IBD may further illuminate the pathophysiology of these disorders.

Adolescent↗
PubMed1997

Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity.

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.

Bile↗
PubMed1997

Vertical lines in distal esophageal mucosa (VLEM): a true endoscopic manifestation of esophagitis in children?

BACKGROUND: We observed an endoscopic abnormally in a group of children with histological esophagitis. We termed this finding "vertical lines in esophageal mucosa" (VLEM). We examined the relationship between the presence of VLEM and significant histologic changes in esophageal mucosal biopsies. METHODS: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The procedure reports, available endoscopic photographs, and histology reports were reviewed to establish the endoscopic and histologic appearance of the esophageal mucosa. Intraepithelial cells were counted in a blind review of 42 randomly selected biopsies. RESULTS: The esophageal mucosa had a normal appearance on 160 endoscopic studies (Group 1) and VLEM were the only mucosal abnormalities in 41 endoscopies (Group 2). Histology was normal in 92 of 160 biopsies (57.5%) from Group 1, and 1 of 41 biopsies (2.4%) from Group 2. Most patients in Group 2 had eosinophilic esophagitis (34 of 41, 83%, specificity 0.85, sensitivity 0.5, p > 0.001) which was of moderate to severe intensity (31 of 34, 91.2%, specificity 0.88, sensitivity 0.73, p < 0.001). CONCLUSIONS: Histology usually demonstrated moderate to severe inflammation when VLEM were present. VLEM may be a highly specific endoscopic feature of esophagitis in children.

Adolescent↗
PubMed1997

Rapid and effective method for preparation of fecal specimens for PCR assays.

We have developed a novel method for the preparation of fecal specimens for PCR assays. Approximately 100 mg of solid stool or 200 microliters of liquid fecal sample was thoroughly suspended in 1 ml of water. Fecal debris was removed by low-speed centrifugation (2,800 x g for 2 min). The supernatant was then boiled for 10 min in a water bath and further clarified by high-speed centrifugation (12,000 x g for 5 min). Fifty microliters of the clarified supernatant was then purified by Sepharose CL-6B spin column chromatography, and a portion of the purified supernatant was used for PCR. By this method, stools containing enterotoxigenic Escherichia coli H10407 were amplified by colonization factor antigen I fimbrial gene PCR, with a sensitivity of 100 organisms per reaction. The method was also effective for processing stool specimens for Clostridium difficile toxin A and B gene PCRs. This method is rapid, effective, and simple to perform and will improve the applications of PCR to stool specimens for diagnostic purposes.

Bacterial Typing Techniques↗
PubMed1997

Stimulation of dog RVLM and A5 area changes sympathetic outflow to vascular beds without effect on the heart.

Studies were conducted in anesthetized, vagotomized dogs while blood pressure; blood flows in femoral, renal, mesenteric, and left circumflex coronary arteries; electrocardiogram; and regional cardiac contractile force were monitored. The ventral surface of the medulla was exposed, and pressor sites in the rostral ventrolateral medulla (RVLM) were mapped by microinjections of L-glutamate. L-Glutamate activation of the RVLM evoked selective effects on different components of the cardiovascular system. Increases of 20-130 mmHg in blood pressure were accompanied by vascular conductance decreases in the femoral (-48 +/- 4%), renal (-30 +/- 4%), and mesenteric (-38 +/- 3%) arterial beds. These effects were without any obvious topography within the RVLM. There were only small or negligible changes in heart rate (HR), cardiac contractile force, and coronary vascular conductance. Thus stimulation of the canine RVLM increased sympathetic tone selectively to structures other than the heart. Stimulation of the ventral medulla in a region that lay rostral to the RVLM and ventromedial to the facial nucleus selectively increased femoral vascular conductance by 103 +/- 33% and decreased vascular conductance in the renal (-20 +/- 5%) and mesenteric (-15 +/- 4%) arterial beds. There was no increase in HR, and the increases in blood pressure were relatively small. Immunohistochemical data led us, tentatively, to identify this rostral area as overlapping part of the A5 area.

Animals↗
PubMed1997

The effect of hip fracture on mortality, hospitalization, and functional status: a prospective study.

OBJECTIVES: The purpose of this study was to prospectively assess the independent effect of hip fracture on mortalìty, hospitalization, and functional status. METHODS: Among 7527 members of the Longitudinal Study of Aging who were over age 70 at baseline, 368 persons with hip fracture occurring between 1984 and 1991 were identified. Median length of follow-up was 831 days. RESULTS: Hip fracture was significantly related to mortality (adjusted hazards ratio [AHR] = 1.83; 95% confidence interval [CI] = 1.55, 2.16) when treated as a time-dependent covariate. This effect was concentrated in the first 6 months postfracture (AHR = 38.93, 95% CI = 29.58, 51.23, vs AHR = 1.17; 95% CI = 0.95, 1.44). Hip fracture significantly increased the likelihood of subsequent hospitalization (adjusted odds ratio = 3.31, 95% CI = 2.64, 4.15) and increased the number of subsequent episodes by 9.4%, the number of hospital days by 21.3%, and total charges by 16.3%. Hip fracture also increased the number of functional status dependencies. CONCLUSIONS: The health of older adults deteriorates after hip fracture, and efforts to reduce the incidence of hip fracture could lower subsequent mortality, morbidity, and health services use.

Activities of Daily Living↗
PubMed1996

Risk factors for nonelective hospital readmissions.

We previously reported a predictive model that identified potentially modifiable risk factors for nonelective readmission to a county hospital. The objectives of this study were to determine if those risk factors were generalizable to a different population. We found that the previously reported risk factors were generalizable, and other potentially modifiable risk factors were identified in this population of veterans. However, further research is needed to establish whether or not the risk factors can be modified and whether or not modification improves outcomes.

Aged↗
PubMed1996

Evaluation of 16S rRNA gene PCR with primers Hp1 and Hp2 for detection of Helicobacter pylori.

The PCR primer set Hp1-Hp2, which amplifies a 109-bp fragment of the 16S rRNA gene of Helicobacter pylori, has been widely used for the detection of H. pylori in clinical specimens. We have examined 34 stool samples and 50 human tissue samples from H. pylori-infected and uninfected patients, five human leukocyte samples, and one human cell line by this PCR method. All of these specimens produced a 109-bp PCR product. When Escherichia coli DNA was used as the template, several nonspecific bands, but not the 109-bp band, were observed. No PCR products were generated when DNA samples from five different fungi were used as templates. These results indicate that this 109-bp PCR product was amplified from the human genome. The 109-bp PCR product generated from various clinical specimens also hybridized with the probe pHp, corresponding to a region internal to the PCR product of Hp1-Hp2. We conclude that the 16S rRNA gene PCR with the primer set Hp1-Hp2 is not specific and cannot be used to detect H. pylori in clinical specimens.

Bacteriological Techniques↗
PubMed1995

Predicting inpatient costs with admitting clinical data.

Hospital cost-containment programs should themselves be cost-effective, targeting high-cost physicians (which requires adjusting for case mix) and patients (which requires early identification). In this study, clinical data available within 24 hours of admission from an electronic medical record system were used to develop statistical models to predict hospital costs. In this retrospective analysis of clinical data and diagnosis-related groups (DRGs), study subjects were 2,355 patients admitted for at least 1 day to the medicine service at an urban teaching hospital with sophisticated electronic medical records. Of these 2,355 patients, 1,663 (71%) had one of the 41 most common DRGs. Predictive models were derived on a random subset of two thirds of the patients and were validated on the remaining third. The following patient data were obtained: admission and prior diagnostic test results, diagnoses, vital signs; demographic data; prior inpatient and outpatient visits; tests and treatments ordered within 24 hours of admission (discretionary data); DRGs; and total inpatient costs (estimated from charges). Diagnosis-related groups explained 24% of the variance in total costs in the derivation patient set and 16% in the validation set. When only nondiscretionary data were used, the models retained only clinical laboratory results and prior diagnoses, explaining 20% of the derivation set variance in total costs and 16% in the validation set. Adding DRGs increased the variance explained in the derivation set to 34%, but decreased to 24% in the validation set. Adding discretionary data substantially increased the explained variance in the derivation and validation patient sets. The models' median predicted costs underestimated true costs by 10% to 13%, with the lowest error in the models using all types of variables. Clinical data gathered during routine clinical care can be used to adjust for case mix and identify high-cost patients early in their hospital stays, when they could be targeted by cost-containment interventions.

Cost Control↗
PubMed1995

Helicobacter pylori infection in recurrent abdominal pain in childhood: comparison of diagnostic tests and therapy.

OBJECTIVE: To determine the role of Helicobacter pylori infection in children with recurrent abdominal pain and the usefulness of serologic tests in screening H pylori infection and monitoring treatment of H pylori-associated gastritis. METHODS: During a 3 year period, we investigated the presence of serum immunoglobulin G (IgG) antibody to H pylori in 456 children using the high-molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non-RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive children of the 218 with RAP syndrome and obtained mucosal biopsies for culture, histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori detection by polymerase chain reaction. RESULTS: Thirty-eight (17.4%) of 218 children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to be negative, and 12 were positive by all five assays. Specimens from 2 children were negative by culture and the CLO test but positive by the other three assays. Specimens from 1 child were negative by histologic analysis but positive by all other tests. The remaining child was positive for anti-H pylori IgG but negative by all of the other four assays. Upper gastrointestinal endoscopy detected 14 children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12 with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were H pylori positive by all five assays, whereas all 12 children with antral nodular gastritis were H pylori positive. Nine of the 12 H pylori-positive children were treated with a combination of bismuth subsalicylate, amoxicillin, and metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori-infected children who did not receive any treatment served as control children, and their IgG levels remained elevated or increased over time. CONCLUSION: The results from our study indicate that screening for the serum IgG antibody to H pylori is a practical method for diagnosing H pylori infection in children, and that serial measurements of the H pylori IgG antibody are useful for monitoring treatment of H pylori because of its high sensitivity and ease of performance. Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to be infected with H pylori, whereas all 12 children with antral nodular gastritis were found to be infected by H pylori. These observations suggest that H pylori infection is more frequently associated with gastritis than with peptic ulcer disease in children, and that H pylori gastritis is a cause of RAP syndrome in children.

Abdominal Pain↗