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Biomedical subjects

L Duffy

Publications and source records attributed to L Duffy.

At least 19 recordsLinked to original sources

Acclimation of a non-indigenous sub-Arctic population: seasonal variation in thyroid function in interior Alaska.

Total, as well as free, T4 and T3 levels were obtained over four seasons for young male infantry soldiers assigned to interior Alaska. Significant seasonal variations were found in both T3 and T4. Total T4 and T3 levels were highest in winter, while free T4 and T3 levels were highest in early spring. Correlations with melatonin levels from a concurrent study showed an association between late day (17.00) mean spot melatonin levels during the preceding summer and T3 levels in winter and spring. Differences in seasonal T4 and T3 levels between indigenous and newly arrived people in the sub-Arctic may be related not only to cold acclimation but also to light.

Acclimatization

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life.

Two hundred children were followed from birth through 2 years of age with nasopharyngeal cultures to determine the normal colonization pattern of nontypeable Haemophilus influenzae. Forty-four percent of the children were colonized on one or more occasions; the acquisition rate was greatest in the first year. Monthly prevalence rates were 11%. Colonization with the initial strain persisted 1-5 months (median, 2). Children carried 1 predominant strain at a time but became colonized with up to 7 different strains (mean, 2.2). Children colonized with a single strain for < or = 2 months produced a greater nasopharyngeal secretory IgA to nontypeable H. influenzae response than did children colonized with different strains (log 2.35 +/- 0.68 vs. 1.89 +/- 0.25 U of P6 secretory IgA/ng/mL of total secretory IgA, P < .01). The duration of colonization with a strain and acquisition of a new strain may be affected in part by the local production of specific secretory IgA.

Aging

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

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

Sulfasalazine and renal tubular function: lack of an effect.

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8-18 years of age, with Crohn's ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary beta 2-microglobulin and n-acetylglucosaminidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary beta 2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.

Adolescent

Ethanol and fetal nutrition: effect of chronic ethanol exposure on rat placental growth and membrane-associated folic acid receptor binding activity.

Rat placental composition and specific folate receptor activity were measured at 20 days gestation in dams exposed to chronic high doses of ethanol (6%, vol/vol) throughout gestation and in isocalorically pair-fed controls. Ethanol-exposed fetuses were smaller (ethanol = 3.28 +/- 0.08 vs. control = 4.01 +/- 0.10 g, p less than 0.001), but their placentae were larger (experimental = 0.534 +/- 0.02 vs. control = 0.399 +/- 0.01 g, p less than 0.001). The increased weight appears to be secondary to hyperplasia as total DNA was increased while the wet/dry, RNA/DNA, and protein/DNA ratios were not different. Despite larger placentae, specific folate receptor activity was significantly reduced in the ethanol-exposed tissue, whether expressed relative to membrane protein, placental weight, or total placental binding. These results confirm that ethanol exposure is placentotoxic and suggest an additional mechanism by which ethanol may lead to intrauterine growth retardation; namely, decreased folate receptor activity.

Animals

Histamine-releasing activity. V. Characterization and purification using high-performance liquid chromatography.

The production of large quantities of the lymphokine(s) histamine-releasing activity (HRA) and its partial purification by Sephadex G-75 and ion-exchange chromatography on carboxymethyl (CM) Sepharose 6B have been detailed (M. A. Lett-Brown, D. O. Thueson, D. E. Plank, M. P. Langford, and J. A. Grant, Cell. Immunol. 87, 434-444, 1984). Two peaks of activity (HRA I and II) were recovered. Preparations of HRA have now been analyzed by high-performance liquid chromatography (HPLC). Thoracic duct lymphocytes stimulated with 200 U/ml streptokinase were used as a source of HRA. Gel-filtration HPLC on a TSK 3000 column separated HRA into two peaks of activity (10,000-20,000 and 1300 Da). Reverse-phase high-performance liquid chromatography using a Nucleosil C-8 column showed that HRA II (the activity eluted at a conductivity of 18-20 mmho on the CM-Sepharose column) eluted as a single sharp peak, the main protein contaminant being cytochrome c, the carrier protein added to enhance the yield of HRA. High-performance liquid chromatography was found to be a useful analytical tool and may be suitable for the large-scale purification of HRA.

Chromatography, Gel