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Biomedical subjects

L Duffy

Publications and source records attributed to L Duffy.

At least 37 records · Page 2Linked to original sources

Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization.

Sixty-eight children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk antibody on nasopharyngeal colonization. Human milk secretory IgA antibody to P6, a highly conserved outer membrane protein of nontypeable Haemophilus influenzae, was measured with the use of an enzyme-linked immunosorbent assay. Nasopharyngeal colonization with nontypeable H. influenzae and the occurrence of otitis media were determined. Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%) had otitis media. Frequency of isolation of nontypeable H. influenzae was directly related to episodes of otitis media (r = 0.35; p = 0.001). The level of human milk anti-P6 secretory IgA antibody was inversely related to frequency of isolation of the organism (r = -0.27; p = 0.026). The average antibody level, expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to children with no colonization of nontypeable H. influenzae was significantly higher than in milk fed to children in whom colonization occurred on multiple occasions (156 +/- 120 vs 69 +/- 50; p = 0.013). Prevention of colonization was most evident during breast-feeding. These data suggest that the protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with nontypeable H. influenzae by specific secretory IgA antibody.

Acute Disease↗

Memory impairment in schizophrenia--a comparison with that observed in the Alcoholic Korsakoff syndrome.

Until very recently, memory impairment was not considered to be a central feature of schizophrenia, except in chronic, deteriorated patients. In this study of a heterogeneous sample of 40 patients with DSM-III-R schizophrenia, episodic memory impairment was found to be prevalent, and in some cases, severe. The degree of memory impairment was not attributable to neuroleptic or anticholinergic medication, or to poor motivation or cooperation. These results, therefore, replicate those reported by McKenna et al. (1990) and Tamlyn et al. (1992), who suggested that the pattern of memory impairment in schizophrenia may conform in important respects to that of the classic amnesic syndrome. However, in a direct comparison of the schizophrenic sample with 18 patients suffering from the Alcoholic Korsakoff Syndrome (AKS), both quantitative and qualitative differences were found to exist between the two groups of patients. In particular, the level of long-term episodic memory impairment was found in the AKS sample to be far greater than that in the schizophrenic group. An interesting possible double-dissociation emerged between the two groups; although demonstrating superior episodic memory functioning, the schizophrenic sample were found to perform significantly more poorly than the AKS sample on a test of semantic memory.

Adolescent↗

Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics.

The relationship between nasopharyngeal colonization with nontypeable H. influenzae and recurrent otitis media was assessed in 157 children followed prospectively from birth through 12 months of age. Forty-nine (31%) became colonized. Nasopharyngeal secretory IgA (sIgA) reactive with the P6 outer membrane protein was detected in all colonized children. Reduction or elimination of the organism was associated with a better mucosal immune response (560 +/- 864 units/ng/mL of sIgA) than was persistence in the nasopharynx (121 +/- 81; P = .04). Forty colonized children (82%) and 61 noncolonized children (56%) developed otitis media (P = .004); colonized children were four times more likely to be classified as otitis prone (P = .003). The frequency of otitis media episodes was directly related to the frequency of colonization (r = .42, P < .01). These results demonstrate a strong relationship between nasopharyngeal colonization patterns and otitis media. The mucosal immune response may be important in elimination of potential pathogens from the respiratory tract.

Age Factors↗

The relationship of RSV-specific immunoglobulin E antibody responses in infancy, recurrent wheezing, and pulmonary function at age 7-8 years.

In order to determine if respiratory syncytial virus (RSV)-specific IgE responses at the time of bronchiolitis in infancy are related to recurrent wheezing and pulmonary function at 7-8 years of age, a cohort of 43 infants was identified at the time of their initial RSV bronchiolitis episode. RSV-specific IgE responses in nasopharyngeal secretions were determined, and patients were then followed prospectively with notation of the number of wheezing episodes and exposure to cigarette smoke at home. At 7-8 years of age the patients underwent skin testing to 7 environmental allergens and pulmonary function testing, including pulse oximetry and methacholine challenge. Pulmonary function following inhalation of bronchodilating agents was compared to baseline pulmonary function results in order to determine if abnormalities of pulmonary function were reversible. Recurrent wheezing following bronchiolitis was associated with the initial RSV-IgE response, as well as with a family history of asthma. Current wheezing at age 7-8 years was associated with 2 or more positive skin tests (P < 0.01), a history of exercise-induced wheezing (P = 0.01), and increased sensitivity to methacholine (P < 0.01). Pulmonary function test results were similar for groups with and without recurrent wheezing following bronchiolitis. For the entire study group, RSV-IgE specific responses were unrelated to pulmonary function, but small airway dysfunction was associated with passive smoking (P < 0.025), and both large airway dysfunction and increased airway reactivity were associated with the number of positive skin tests (P < 0.025). Reduced small airway function improved following bronchodilator inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Renal biopsy in children with asymptomatic hematuria or proteinuria: survey of pediatric nephrologists.

The decision to perform a renal biopsy on children with asymptomatic hematuria or proteinuria remains a problem for clinicians. To assess the current opinion of 349 pediatric nephrologists on this issue, case summaries of a 9-year-old boy with 20 urinary red blood cells per high power field without proteinuria and a 9-year-old boy with 2+ proteinuria (600 mg/day) without hematuria were distributed to each specialist. Seventy-three percent (n = 256; 3:1, male:female) responded. Five percent would biopsy the child with asymptomatic hematuria. The main reasons were academic interest, parental pressure for a diagnosis/prognosis and concern for future economic impact on the child (i.e., life insurance). The determinations to biopsy for hematuria were not related to age or sex of the nephrologist. In contrast, 38% (n = 96) of the pediatric nephrologists would perform a biopsy on the child with proteinuria. The major reasons for biopsy were academic interest and potential for drug therapy. With a normal history, physical examination and laboratory/radiographic evaluation, the vast majority of pediatric nephrologists in North America support a conservative approach to the child with asymptomatic hematuria or proteinuria.

Adult↗

Detection of Ureaplasma urealyticum by polymerase chain reaction in the urogenital tract of adults, in amniotic fluid, and in the respiratory tract of newborns.

On the basis of the nucleotide sequence of the urease genes of Ureaplasma urealyticum serotype 8, polymerase chain reaction (PCR) primers were selected, evaluated for specificity and sensitivity, and tested for their ability to detect U. urealyticum in the adult urogenital tract, amniotic fluid, and endotracheal aspirates of newborns. All 14 reference serotypes of U. urealyticum were detected with equal sensitivity (1-10 cfu), whereas multiple strains of 12 other mycoplasma species found in humans as well as eukaryotic DNA were not detected. A total of 638 clinical specimens was evaluated. Results indicate that PCR is equal to if not more sensitive than culture for detection of U. urealyticum. Faster detection of U. urealyticum by PCR (< 24 h) compared to culture (2-5 days) will be particularly important in management of very low birth-weight infants in whom this organism has been shown to be a significant cause of meningitis, respiratory disease, and death. This method of detection will also be helpful in further determining the role of this organism in intraamniotic infection and premature birth.

Adult↗

Use of the polymerase chain reaction for detection of Mycoplasma fermentans and Mycoplasma genitalium in the urogenital tract and amniotic fluid.

In an attempt to further define the natural history of Mycoplasma genitalium and Mycoplasma fermentans infections in humans, we used cultures and the polymerase chain reaction (PCR) to determine whether these organisms were present in the urethra and cervix of sexually active adults and in the amniotic fluid of women whose membranes were intact and collected at the time of cesarean delivery (to preclude cervical contamination). M. genitalium was detected by PCR but not by culture in 11% of patients with urethritis or cervicitis. It was not detected by either PCR or culture in the 232 amniotic fluid samples analyzed. In contrast, M. fermentans was not detected by either method in patients with urethritis or cervicitis but was detected by PCR in 4 of 232 amniotic fluid samples tested. These results indicate that in these four cases M. fermentans was transferred transplacentally. Histological evidence of chorioamnionitis was present in two of the four patients, a finding suggesting that M. fermentans may be a cause of chorioamnionitis. These results must be confirmed by other investigators, and further studies should be undertaken to determine the potential clinical significance of M. fermentans infection.

Adolescent↗

Long-term immunity to poliovirus in children immunized with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines.

Eighty-six children who completed immunization with the two trivalent poliovirus vaccines, live attenuated (OPV) and enhanced potency inactivated (EIPV), in one of four schedules (OPV-OPV-OPV, EIPV-EIPV-EIPV, EIPV-OPV-OPV, and EIPV-EIPV-OPV) at 1 year of age were monitored serologically over the subsequent 4 years and challenged with OPV at 5 years of age. Each of the immunization groups exhibited an initial 10- to 100-fold decline in neutralizing antibody to poliovirus types 1, 2, and 3 during the first 2 years of follow-up; thereafter antibody titers stabilized. The EIPV-EIPV-OPV group maintained the highest antibody levels throughout the observation period, including the response to OPV challenge at 5 years of age. These data suggest that immunization with OPV, EIPV, and combinations of the two vaccines confers long-term immunity. Optimal systemic immunity was associated with two or more doses of EIPV.

Antibodies, Viral↗

Effect of concurrent viral infection on systemic and local antibody responses to live attenuated and enhanced-potency inactivated poliovirus vaccines.

OBJECTIVE: To determine the effect of an asymptomatic nonpolioviral infection on the immune response to poliovirus vaccines. DESIGN: Open comparative trial. SETTING: Well-child clinic at The Children's Hospital of Buffalo, NY. PARTICIPANTS: Twenty-seven healthy infants infected with nonpolioviruses and 27 healthy controls matched for age and vaccine group. INTERVENTIONS: Trivalent oral attenuated poliovirus vaccine or enhanced potency inactivated vaccine administered at ages 4 and 12 months. MEASUREMENTS/MAIN RESULTS: Neutralizing antibody to poliovirus serotypes 1, 2, and 3 were determined in the serum and nasopharyngeal secretion samples obtained at ages 4, 5, 12, and 13 months. The IgA antibody titers for polioviruses 1, 2, and 3 were measured in nasopharyngeal secretion samples during the same periods. Antibody responses to poliovirus vaccines were similar in coinfected subjects and healthy controls at ages 5 and 13 months, except for serum neutralizing antibody that was significantly elevated in the controls compared with coinfected subjects (geometric mean [+/- SD] antibody titers, 12.7 +/- 1.6 vs 11.5 +/- 1.7). Concurrent viral infections affected the immune response in recipients of the oral poliovirus vaccine and the enhanced-potency inactivated poliovirus vaccine similarly. The immune response to polioviruses 1 and 3 were more adversely affected by coinfection than was the immune response to poliovirus 2. CONCLUSION: Concurrent asymptomatic viral infections minimally impaired the immune response to poliovirus vaccines. The adverse effects of coinfection were considered clinically insignificant.

Antibodies, Viral↗

Pancreatoduodenectomy with preservation of the stomach and pylorus: a safe and effective alternative in children.

The time-honored surgical approach to resectable tumors of the head of the pancreas or distal common bile duct has been a Whipple operation for adults and children. In recent years, pylorus-preserving pancreatoduodenectomy has been used for adults. The postoperative physiological advantages may be enhanced in children, and for this reason the pylorus-sparing approach was used in a 15-year-old girl with a tumor of the distal common duct. The pylorus-preserving pancreatoduodenectomy was safe and effective in this patient and should be considered for children with resectable tumors of the distal common bile duct and pancreatic head.

Adolescent↗

Failure of cryopreserved homograft valved conduits in the pulmonary circulation.

BACKGROUND: This study evaluates our experience with the cryopreserved homograft valved conduit used for reconstruction of the pulmonary circulation in patients with congenital heart disease. METHODS AND RESULTS: Between July 1, 1985, and December 31, 1990, 219 patients had cryopreserved homograft extracardiac valved conduits placed in the pulmonary circuit. Average age at operation was 7.2 years. Of these, 132 patients had a pulmonary homograft, and 87 had an aortic homograft. Twenty-four patients (11%) died in hospital. Hospital survivors (n = 195) have been followed an average of 29.8 months (SD, +/- 18.4 months). Fourteen patients died during follow-up, almost all related to the complexity of their original cardiac malformation. Thirty-two patients (15%) have required reoperation for conduit-related problems. Actuarial freedom from conduit reoperation is 55 +/- 12% at 5 years. The most common indication for reoperation was calcific stenosis (n = 27). Other indications for reoperation were pseudoaneurysm (n = 2), conduit infection (n = 2), and pulmonary insufficiency (n = 1). Reoperation rate for patients with aortic homografts (16 of 87) compared with that for pulmonary homografts (16 of 132) was not significantly different by the actuarial method. CONCLUSIONS: Long-term function of cryopreserved homograft valved conduits in the pulmonary circulation is disappointing.

Actuarial Analysis↗

Neuronal intestinal dysplasia: quantitative diagnostic criteria and clinical management.

Neuronal intestinal dysplasia (NID) clinically resembles Hirschsprung's disease but is characterized by hyperplasia rather than aganglionosis of the intramural plexus. Surgical intervention is common. We report the 5-year follow-up of an infant with the mixed form of NID managed medically and a method by which NID can be quantified histologically. Hyperganglionosis was determined by counting the number of ganglia per high-power field and the number of ganglion cells per ganglia from at least two biopsy specimens. The patient's biopsies and biopsies from "normal" and "inflamed" patients were compared. Normals contained 0.68 +/- 0.28 (mean +/- SD) ganglia per high-power field and 2.16 +/- 0.31 ganglion cells per ganglion. The inflamed biopsies were similar, 0.69 +/- 0.38 ganglia per high-power field and 2.63 +/- 0.40 ganglion cells per ganglion. The patient's initial rectal biopsy revealed 7.6 ganglia per high-power field and 3.8 ganglion cells per ganglion. Management of the patient included saline colonic irrigations and hyperalimentation with gradual reinstitution of breast-feeding. Clinical improvement was associated with normalization of manometry and biopsy findings, a phenomenon not documented previously in the literature. Irrigations were stopped at age 9 months, and the child is now asymptomatic.

Biopsy↗

Instability of performance on cognitive tests in infants and young children with Down's syndrome.

Stability of cognitive performance in assessment situations was investigated in a group of 18 children with Down's Syndrome (DS) aged 6 months to 4 years. Two widely used tests of early cognitive development were presented: the Mental Scale of the Bayley Scales of Infant Development and a series of Piagetian object concept tasks. Both sets of tasks were presented in the same testing session, with testing repeated one to two weeks later. Both qualitative and quantitative aspects of performance were recorded. Even when overall scores were similar, patterns of pass/fails were very different in the two testing sessions. Successes showed poor stability over sessions with fails often occurring by default, the result of a refusal to engage fully in a particular task. This pattern of results suggests: (1) that single-session testing may not adequately assess cognitive status in DS children; (2) that the relationship between performance and competence may be unstable in such children, and (3) that "slow development" theories may not adequately describe cognitive development in young children with DS.

Achievement↗

Partial sequence of MAP2 in the region of a shared epitope with Alzheimer neurofibrillary tangles.

A 3.3-kilobase DNA complementary to human microtubule-associated protein 2 (MAP2) was sequenced by the dideoxy method. The 3' end terminates at an internal EcoRI site before the polyA tail. Due to the arrangement of the cDNA insert in the lambda gt11 vector, the MAP2 fragment is not fused to beta-galactosidase when expressed. The Chou Fasman algorithm for the initial 58 amino acids from the first in-frame methionine predicts an alpha helix. Beyond this point, a series of turns is predicted until amino acid 160. The frequent presence of basic residues in proximity to serines or threonines is consistent with multiple phosphorylation sites. The minimum specificity determinant for Ca2+/calmodulin-dependent kinase is repeated 13 times. The sequence of a region containing a MAP2 epitope that is shared with the Alzheimer neurofibrillary tangle was determined by DNase treatment of the cDNA and antibody selecting the small resultant clones in a lambda gt11 sublibrary. Likewise, a MAP2 epitope that is not shared with the neurofibrillary tangle also has been located. Both epitopes are in the projection portion of the molecule. A bovine MAP2 cyanogen bromide fragment, which contains the epitope shared with the neurofibrillary tangle, is partially insoluble under aqueous conditions, probably due to the aggregation of oppositely charged residues. Thus, rapid cleavage of MAP2 to small peptides is probably necessary in vivo to prevent the aggregation of larger cleavage fragments.

Alzheimer Disease↗

Berry aneurysms, cirrhosis, pulmonary emphysema, and bilateral symmetrical cerebral calcifications: a new syndrome.

Familial idiopathic nonarteriosclerotic cerebral calcification (FINCC) constitutes a rare but pathologically well defined disorder. Thus far, central nervous system symptoms and signs have been the only recorded expression of this disease. Autosomal dominant and autosomal recessive inheritance have both been postulated as cause. We describe three sibs who had symmetrical cerebral calcifications, but three also had cirrhosis and pulmonary emphysema; two had congenital cerebral aneurysms. All were male and of short stature; they also had delayed development and seizures, and two had other neurologic deficits. One sib died at age 3 years of hepatic failure and portal hypertension. Ruptured cerebral aneurysms led to the death of the other two boys at ages 8 and 13 years. The cerebral calcifications symmetrically involved the basal ganglia and thalami, the dentate nucleus, and the cortical and subcortical areas of the cerebrum. The liver was studied by sequential biopsies in two of the children and in all three by autopsy. Fatty degeneration and portal fibrosis preceded a periportal and micronodular cirrhosis. Severe bilateral pulmonary emphysema was present in one sib at age 12 years, whereas all three had bullae and cysts at autopsy. Ruptured left middle cerebral artery aneurysms were demonstrated in two sibs, and one also had aneurysms of the anterior and posterior communicating arteries. We conclude that in this family FINCC is a complex pleiotropic mendelian mutation, either of autosomal or X-linked recessive nature, whose basic pathogenesis remains unknown but may involve a metabolic defect. This form of FINCC may be a previously undescribed syndrome or a form of FINCC in which extraneural manifestations were previously overlooked.

Adolescent↗