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Biomedical subjects

M L Williamson

Publications and source records attributed to M L Williamson.

14 recordsLinked to original sources

Regeneration of immunosorbent surfaces used in clinical, industrial and environmental biosensors. Role of covalent and non-covalent interactions.

The durability and regeneration of antibodies immobilized to commercial immunosorbents were investigated by monitoring Ag-Ab dissociation. Solutions consisting of 0.01 M hydrochloric acid (HCl), 10% propionic acid, 50% ethylene glycol and 10% SDS in 6 M urea were used in the evaluation of antigen dissociation from antibody covalently immobilized to glass and polystyrene beads, microtiter plates and Immobilon filters. RAH-IgG, used as a model antibody, bound strongly to all covalent surfaces. However, on adsorption to Nunc-1 microtiter plates, 25-60% of RAH-IgG was removed by all dissociating solutions. Covalent binding to Sanger beads was weakest relative to other covalent surfaces, exhibiting 30% and 65% detachment with ethylene glycol and SDS in urea, respectively. Although all four solutions dissociated antigen from surface-bound antibody, HCl and propionic acid were more effective on most surfaces. The antibody remained functional following antigen dissociation and reassociated to nearly 100% on all surfaces except Sanger beads and Nunc-1 microtiter plates. This study was initiated to evaluate regeneration and reuse of microelisa plates and emerging biosensors as a means of reducing routine laboratory analysis costs. Data are presented to demonstrate the reusability of microtiter plates in ELISAs following antigen dissociation from covalently bound antibody.

Antigen-Antibody Complex

Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age.

Early-treated PKU children were compared to their matched non-PKU sibling controls on Wechsler Intelligence Scale for Children (WISC) and Wide Range Achievement Test (WRAT) results at age 8. Fifty-five PKU children had mean WISC Full Scale IQ score of 100, in comparison to a mean of 107 for their matched sibling controls (p = 0.001). Treatment parameters significantly correlated with sibling-PKU IQ score differences included maximum diagnostic phe level (r = 0.244, p = 0.036) and phe levels at age 6 (r = 0.329, p = 0.007) and at age 8 (r = 0.489, p less than 0.0005). Fifty PKU subjects scored significantly lower than their matched sibling controls on standard scores of the WRAT Reading (102 vs. 107, p = 0.016) and Arithmetic (96 vs, 101, p = 0.006) subtests, and lower, but not significantly so, in Spelling (100 vs. 103, p = 0.145). When the sample was grouped according to diet status at age 8, on-diet PKUs scored at or above the level achieved by their siblings on all three scales of the WISC and all three WRAT subtests, whereas the off-diet group scored from 7 to 13 points below their siblings on all measures. These results suggest that PKU children should restrict phe intake at least through their school years.

Child

Physiologic stress reduction by a local anesthetic during newborn circumcision.

To evaluate the effectiveness of the dorsal penile nerve block in reducing the stress of circumcision upon newborns, physiologic measurements in 30 healthy full-term infants (including transcutaneous oxygen levels, crying time, heart rate, and respiratory rate) were monitored continuously before, during, and after the operation. Infants receiving the dorsal penile nerve block with lidocaine (1% Xylocaine) (N = 20) experienced significantly less stress, as evidenced by smaller decreases in transcutaneous oxygen pressure levels, less time spent crying, and smaller increases in heart rate, than infants circumcised in an identical manner without anesthetic (N = 10). No complications resulted from injection of the local anesthetic or from the circumcision procedure itself. Inasmuch as dorsal penile nerve block has a low complication rate, is simple to learn, and adds little time or expense to the overall procedure, and if it proves to be as effective clinically as the physiologic data indicate, the dorsal penile nerve block should be considered for every infant undergoing circumcision.

Anesthesia, Local

Preliminary report on the effects of diet discontinuation in PKU.

A collaborative study of diet discontinuation in children with PKU was initiated in 1973. Children treated with the phenylalanine-restricted diet since early infancy were randomly assigned to continue or discontinue dietary therapy at age 6 years after parental consent was obtained. The 115 children participating in this study range in age from 8 to 13 years. At 6 years of age, the IQ of continuers and discontinuers was 101 and 97, respectively. At 8 years, WISC Full-Scale IQ scores adjusted for mean differences on the 6-year Stanford-Binet IQ were 101 for continuers and 98 for discontinuers (P = 0.075). School performance measured by the Wide Range Achievement Test showed significant differences on reading (3.9 vs 3.2) and spelling (3.3 vs 2.9) grade placement, although scores were above actual grade placement (2.7 vs 2.6) for both groups. Continuers and discontinuers were not different in arithmetic scores, with performance at grade placement of 2.7 and 2.6 respectively. Although these data are preliminary in nature, they suggest that subtle changes in cerebral function may occur in children with PKU in whom the phenylalanine diet has been discontinued.

Age Factors

Correlates of intelligence test results in treated phenylketonuric children.

The Collaborative Study of Children Treated for Phenylketonuria was initiated in 1967. The data presented are based on findings in 132 children treated from near birth to 6 years of age. Two treatment groups were randomly formed. The target for blood phenylalanine was 1.0 to 5.4 mg/100 ml for group 1 and 5.5 to 9.9 mg/100 ml for group 2. Although mean blood phenylalanine levels for both groups initially fell within the prescribed ranges, a steady increase over time resulted in mean six year levels of 11.4 mg/100 ml and 13.0 mg/100 ml for the two groups, respectively. Because it was not possible to maintain the prescribed differences in blood phenylalanine levels between the two groups, they were combined for further analyses. The mean IQ of the total sample at age 6 years was 98 on the Stanford-Binet Intelligence Scale. Multiple regression analysis showed that, among selected treatment and psychosocial factors, the most important predictors of IQ for 6-year-old children were: (1) mothers' intellectual ability (as measured on the Wechsler Adult Intelligence Scale); (2) age at which the subjects were first treated; and (3) how well the subjects adhered to the phenylalanine-restricted diet. It was concluded that optimal early treatment will result in normal levels of intelligence at 6 years of age.

Age Factors

The diagnosis of phenylketonuria: a report from the Collaborative Study of Children Treated for Phenylketonuria.

One hundred ninety-five infants who met diagnostic criteria for enrollment in the Collaborative Study of Children Treated for Phenylketonuria (PKU) underwent a standard three-day challenge with 180 mg/kg/day of phenylalanine for confirmation of diagnosis. A sustained rise in serum phenylalanine levels of greater than 20 mg/dl was observed in 166 infants (85.1%), compatible with the diagnosis of classical PKU. In the remaining 29 infants (14.9%), the serum phenylalanine concentration either did not reach 20 mg/dL or, having achieved this level, subsequently declined below this point by 72 hours. It was agreed that these 29 patients had variant PKU and they were dropped from the Collaborative Study. We recommend that all infants diagnosed as having classic PKU undergo a challenge to confirm the diagnosis and need for continued treatment.

Humans

Diet, genetics, and mental retardation interaction between phenylketonuric heterozygous mother and fetus to produce nonspecific diminution of IQ: evidence in support of the justification hypothesis.

The justification hypothesis postulates that an individual genetically deficient in the synthesis of any of the 12 nonessential amino acids requires that amino acid in the diet just as a normal individual requires any essential amino acid. The deficiency of that single amino acid causes diminished protein synthesis. The hypothesis proposes that mental retardation develops during the late stage of fetal development, when the brain is growing most rapidly, as a result of the inability of the mother to deliver an appropriate amount of that nonessential amino acid to her fetus who, in turn, is unable to correct for this deficiency due to his genetic constitution. A paradigm is provided by the disease phenylketonuria in which the homozygote lacks the enzyme for synthesis of the nonessential amino acid tyrosine. By measuring the appearance of tyrosine in the plasma after an oral dose of phenylalanine, it is possible to show differential capability among siblings of known phenylketonuric children, in the expected Mendelian ratio. The mean IQ of the two-thirds of the siblings who were least able to convert phenylalanine to tyrosine (presumably heterozygotes) was 10 points lower than the mean IQ of the "normals," who were most able to synthesize tyrosine. The difference is statistically significant (P <0.01). The mean maternal IQ was halfway between that of the heterozygote group and that of the normal group, confirming the prediction of maternal-fetal interaction.

Diet

Intellectual assessment of 111 four-year-old children with phenylketonuria.

Of the 216 children with phenylketonuria (PKU) who were initially enrolled in the Collaborative Study of Children Treated for Phenylketonuria, 203 were placed on dietary therapy between 3 and 92 days of age. Of these, 111 are now at least 4 years of age and constituted the sample for the present analysis. Their mean IQ on the Stanford Binet Intelligence Scale was 93 (1972 norms). The children assigned to two treatment groups based on "moderate" and "low" serum phenylalanine levels were comparable on their IQs at age 4, although many of the children could not be maintained in the specified categories. Females scored a significantly higher mean IQ than males (97 vs 90). Those children for whom dietary treatment was initiated during the first month of life scored a mean IQ of 95, compared with 85 for those initially treated from 31 to 65 days. However, the interpretation of dietary inception data may have been contaminated by familial and psychosocial factors. The PKU Collaborative Study is still in progress in 15 clinics located in 11 states.

Child, Preschool

Sexual adjustment after hysterectomy.

The impact of hysterectomy or oophorectomy is not limited to problems of altered body image and depression. Uterus removal, compounded by the possible loss of estrogen and androgens, alters sensations and reactions that had been part of a woman's sexual response. Sexual and marital adjustment after hysterectomy depends on anticipatory guidance regarding decreased libido, physical changes, loss and grief reactions, and the possible complications of cancer therapy. Nurses can affect outcomes through straightforward counseling and education.

Adaptation, Psychological

Reducing post-catheterization bladder dysfunction by reconditioning.

The purpose of this study was to determine the effect of reconditioning upon bladder dysfunction caused by prolonged catheterization. Eight women undergoing surgery with baseline residual urine volumes (RUVs) not greater than 25 ml and catheterization durations of 36 to 106 hours qualified as subjects. Immediately prior to catheter removal, the four treatment group subjects received reconditioning, a procedure in which their catheters were clamped for three hours followed by five minutes of urinary drainage. This cycle was repeated twice more, totaling nine hours, ten minutes. The four control group subjects received no reconditioning. After catheter removal, reconditioned subjects resumed natural micturition significantly sooner than non-reconditioned subjects (t = -2.82, df = 6, p less than 0.05). A t test showed no significant differences between the groups in post-indwelling catheterization RUVs following the first micturition, probably due to the small number of subjects, since the control group's mean post-catheterization RUV increased to a physiologically abnormal level (42.25 ml), while the reconditioned group's mean RUV stayed within normal limits. This study should be repeated to test for statistical significance in larger samples.

Adult