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Biomedical subjects

M L Mitchell

Publications and source records attributed to M L Mitchell.

At least 19 recordsLinked to original sources

Topical iodine and neonatal hypothyroidism.

OBJECTIVES: To determine whether skin care practices with iodine-containing disinfectants are putting patients in the neonatal intensive care unit at risk for primary hypothyroidism. Cutaneous exposure to povidone-iodine antiseptic solutions may be a cause of primary hypothyroidism in neonates. DESIGN: Prospective pilot study. SETTING: Level III neonatal intensive care unit of a university-affiliated hospital. PARTICIPANTS: Sequential sample of 47 medial and surgical patients admitted to the neonatal intensive care unit who received cutaneous povidone-iodine applications in preparation for invasive or surgical procedures. METHODS: Seven to 10 days after iodine exposure, capillary blood samples were obtained on filter paper blots for thyroid function testing and urine samples were collected to determine quantitative iodine concentrations. A plasma creatinine level was determined for each subject. RESULTS: A total of 47 patients were enrolled. The gestational ages of subjects ranged from 26 to 41 weeks (mean, 33.6 weeks); the male-to-female ratio was 28:19; and the birth weights ranged from 0.7 to 5.1 kg(mean, 2.42 kg). The thyroxine level ranged from 20 to 187 nmol/L (1.6 to 14.6 micrograms/dL) (mean, 102 nmol/L [7.9 micrograms/dL];reference, > or = 90 nmol/L [> or = 7 micrograms/dL]; and the thyrotropin level ranged from 0.1 to 16.5 mU/L (mean, 6.4 mU/L; reference, < 20 mU/L). The mean uridine iodine concentration was 2798.0 micrograms/dL (reference, < 40 micrograms/dL), and the mean plasma creatinine level was 60 mumol/L (0.69 mg/dL) (reference, < or = 50 mumol/L [ < or = 0.6 mg/dL] for males and < or = 40 mumol/L [ < or = 0.5 mg/dL] for females). CONCLUSIONS: There was no documentation of primary hypothyroidism in our subjects despite elevated urine iodine levels. While it is still possible that patients who receive long-term iodine exposure in other settings (eg, cardiac catheterization) are at risk for primary hypothyroidism, our study suggests that the amount of iodine absorbed through routine neonatal intensive care unit procedures does not substantially alter thyroid function during the first 10 days of life. An important confounding variable is that seven patients were receiving dopamine hydrochloride infusions and four were receiving dexamethasone phosphate at the time of sample collection. We therefore cannot rule out the possibility that these medications masked a thyrotropin level elevation that would have occurred in a primary hypothyroid state. We discuss implications for the interpretation of the results of neonatal thyroid function tests.

Administration, Cutaneous

Measurement of thyroglobulin in newborn screening specimens from normal and hypothyroid infants.

BACKGROUND AND OBJECTIVE: Thyroglobulin (Tg) has been found in varying concentrations in infants and children with congenital hypothyroidism. Our primary goal was to ascertain whether Tg in filter paper blood specimens used for routine newborn screening would be a useful adjunct in the early diagnosis of newborn children with congenital hypothyroidism. Our secondary objective was to correlate the results of the Tg determinations with the results of thyroid scintigraphy in the same cohort of infants with congenital hypothyroidism. DESIGN: An RIA kit with high sensitivity for the measurement of Tg in serum was modified for use with filter paper blood specimens. Results of thyroid scintigraphy were obtained from the family physicians on 10 infants with ectopic thyroid glands and 18 who were considered to be athyreotic. MEASUREMENTS: Determinations of Tg were carried out retrospectively on newborn screening filter paper blood specimens from 61 full-term normal infants and 42 newborns with confirmed congenital hypothyroidism. RESULTS: Thyroglobulin concentrations during the first week of life in the normal controls ranged between 17 and 160 micrograms/l, with a median of 66 micrograms/l. Tg values for infants with ectopic thyroid glands ranged between 38 and 282 micrograms/l, with a median of 160 micrograms/l, with a median of 66 micrograms/liters. Tg values for infants who were considered athyreotic had Tg values ranging between undetectable and 104 micrograms/l with a median of 15 micrograms/l. Fifty per cent of the athyreotic patients and 50% of patients with ectopic thyroid glands had Tg values above or below the normal range and thus fell within the diagnostic category of hypothyroidism on the basis of Tg alone. Fifty per cent of patients who were considered athyreotic by scintigraphy had Tg concentrations ranging from 20 to 104 micrograms/l. CONCLUSION: These studies have shown that thyroglobulin can be measured in the same filter paper blood specimens used for routine newborn screening. Estimation of thyroglobulin in screening specimens from hypothyroid and normal infants indicated that some infants with congenital hypothyroidism could be identified solely on the basis of the thyroglobulin concentration. Comparison of the result of scintigraphy with thyroglobulin levels in the same hypothyroid patients suggested that thryoglobulin provided a more reliable marker for the presence or absence of the thyroid gland than did scintigraphy.

Biomarkers

Early minimal feedings promote growth in critically ill premature infants.

Critically ill premature infants requiring mechanical ventilation and an umbilical artery catheter usually do not receive enteral feedings during the acute phase of their illness. We studied the safety and benefit of early minimal enteral feedings during this time in a prospective, controlled, and randomized study. Twenty-nine infants were randomly assigned to receive only standard intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h), beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings were begun in both groups at the resolution of the acute phase of the illness and advanced by protocol. The two groups were of comparable birth weight, gestational age, and Apgar scores. There were no significant differences in the episodes of feeding intolerance. Two infants in the NPO group developed clinical signs of necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured weekly until 30-60 days of age and were not different between the two groups. The early-feeding group required fewer days to reach 120 ml/kg/day enteral intake (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30 of life the early-feeding group was 223 +/- 125 g above birth weight, while the NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We conclude that early minimal feedings in critically ill very-low-birth-weight infants requiring mechanical ventilation are well tolerated and result in reduced time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by day 30 of life.

Amine Oxidase (Copper-Containing)

Interdepartmental quality assurance using coded autopsy results.

A system of reporting discrepancies between antemortem and postmortem diagnoses was devised for use in interdepartmental quality assurance at a large community medical center. Between 1988 and 1991, 213 autopsies comprising 6% of deaths were coded using the system of Battle et al. (1) and distributed to the quality assurance committees of clinical departments. A major discrepancy was found in 11.7% (95% confidence interval; 6.8 to 18.4%) of adult cases. The discrepancy rate tended to increase with increasing patient age, but there was no significant effect due to patient sex, race, hospital of origin, clinical department of origin, whether the autopsy was restricted to examination of only part of the body, or whether the patient died in or out of the hospital. The possible uses of the quality assurance system and problems encountered with its implementation are discussed.

Abstracting and Indexing

A comparison of skeletal muscle morphology with training between young and old Fischer 344 rats.

Muscle mass, fiber area, total fiber number, fiber population and capillarity were assessed in 6- and 25-month-old animals trained by treadmill running at 75% mean maximal capacity for 10 weeks. Serial cross-sections were stained for ATPase activity to differentiate fiber types and expose capillaries. Aging and training effects were demonstrated in maximal running speed and endurance running time. Soleus muscle mass increased in the aged, however, soleus and EDL total fiber number were declining. When adjusted for muscle weight, a significant reduction existed in fiber number for the aged soleus. Fiber area increased in the old soleus compared to young. All changes in the EDL were specific to the deep region. While there was a tendency for the capillaries/fiber and fiber area to be higher with training in the Type I fibers of the soleus, it was only significant for the young animals. Thus, while the majority of variables that showed a training effect did so across both age groups, this was not the case for vascularity. Age-associated changes in muscle morphology appear to be both muscle and fiber specific.

Aging

Case report 697: Neuropathic arthropathy of the shoulder with no identified cause.

Two cases of neuropathic disease of the shoulder without evidence of a neurological disorder are described. The absence of any neurological disorder led to the cases being initially mistaken for primary neoplasms of bone, lending support to the vascular theory of pathogenesis of this lesion. Careful attention to the radiographic features and knowledge that a neurological disorder need not be present should lead to the correct diagnosis.

Adult

Prevalence of thyroid deficiency in pregnant women.

OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.

Adult

Gender differences in the development of relationships during late adolescence.

Until recently, inadequate measures of affiliation need and relationship closeness hindered investigations into the social development of adolescents. For example, assumptions about gender differences (Douvan & Adelson, 1966; Gilligan, 1982) and age-related changes (Dunphy, 1972; Erikson, 1968; Newman & Newman, 1976) in affiliation need and relationship closeness have remained virtually untested. To better understand adolescent social behavior and test these assumptions, recently developed measures of affiliation need and interpersonal closeness were used to examine seventy-four 18- to 20-year-olds. In support of Erikson's theory, need for social comparison declined with age for both sexes. However, in support of Gilligan's theory, not only were females more attached to their partners, but these gender differences were most pronounced for the 18-year-olds. Finally, Dunphy's (1972) assumption that adolescents' need for stimulation peaks around age 18 or 19 and then declines, and Newman and Newman's (1976) position that need for emotional support declines in later adolescence, held true--but only for females.

Adaptation, Psychological

Infrared spectroscopic investigations of pulmonary surfactant. Surface film transitions at the air-water interface and bulk phase thermotropism.

The molecular structure of the phospholipid component of intact pulmonary surfactant isolated from bovine lung lavage has been examined by Fourier transform infrared spectroscopy. Two different physical states of the surfactant were examined by means of different infrared spectroscopic sampling techniques. Transmission infrared experiments were used to study the surfactant in the bulk phase. In these experiments, the thermotropic behavior of the bulk surfactant was monitored by temperature-induced variations in the phospholipid acyl chain CH2 stretching frequencies. A broad phase transition (confirmed by differential scanning calorimetry) was noted with an onset temperature near 15 degrees C and a completion temperature near 42 degrees C. In addition to the bulk transmission experiments, external reflection infrared spectroscopy was used to examine surfactant films in situ at the air-water interface. As surface pressure was increased from 0 to 43 dyn/cm, a gradual and continuous decrease in the CH2 stretching frequency was noted for the surfactant. Thus, under surface pressures which correspond to large lung volumes in vivo, the surfactant acyl chains exist mostly in the ordered (trans) configuration. The frequency shift in the CH2 stretching mode is consistent with a continuous ordering of the acyl chains upon compression over the pressure range 0-43 dyn/cm, and implies that a weakly cooperative phase transition occurs in the hydrocarbon region of the surface film. The surface film transition is especially noted in the pressure-area curve of the surfactant and approximates in two dimensions the broad thermotropic phase transition of the bulk phase surfactant. Substantial differences were observed between the response to surface pressure changes of intact surfactant compared with the main surfactant phospholipid, 1,2-dipalmitoyl-sn--glycero-3-phosphocholine. The changes in response are attributed to the presence of additional surfactant components. The current work demonstrates the ability of infrared spectroscopy to obtain structural information on the surfactant in physical states that directly relate to those in vivo.

1,2-Dipalmitoylphosphatidylcholine

The relationship of insulin-like growth factor-I to total thyroxine in normal and low birth weight infants.

IGF-I concentrations were determined by RIA in eluates of dried blood collected on filter paper from infants who ranged in age from 3 to 21 d. The infants were separated into normal (greater than 2.5 kg) and low (less than 2.5 kg) birth wt groups and further subdivided on the basis of normal (greater than 83.7 nmol/liter) or low (less than 64.4 nmol/liter) levels of thyroxine. Both the normal and low birth wt groups whose blood thyroxine was in the normal range had similar mean IGF-I values during the 1st wk of life that were significantly higher (p less than 0.05) than those of either the normal or low birth wt groups whose thyroxine concentrations were below normal. Infants older than 1 wk of age with normal birth wt and normal thyroxine levels had significantly greater (p less than 0.05) mean IGF-I values than those of any of the other groups. Infants in the low birth wt-normal thyroxine group exhibited modest increases in IGF-I levels after the 1st wk of life that were significantly greater (p less than 0.05) than those found in the low birth wt-low thyroxine infants. These studies have demonstrated that IGF-I concentration is correlated positively with total thyroxine and with birth wt and that the latter is confounded by the former.

Humans

A technique for monitoring mammalian cell growth and inhibition in situ via Fourier transform infrared spectroscopy.

A single culture of Chinese hamster ovary cells was grown on germanium attenuated total reflectance (ATR) crystals and continuously monitored in situ via ATR/Fourier transform infrared (FT-IR) spectroscopy for approximately 60 h. The cells were seeded into a specially designed flow cell which controlled physiological conditions, flow rate, and addition of growth medium or metabolic inhibitors. Infrared spectra were taken at 20-min intervals until a confluent monolayer was formed. Several strong bands are evident in the spectra which can be generally ascribed to molecular features of cellular components. Cell growth kinetics were measured as a function of infrared band intensity over time and exhibited the normal lag phase, logarithmic growth, and stationary phase on reaching confluence. Spectra of growing cells, normalized to the area under the spectral region 1800-1000 cm-1, were subtracted from reference spectra of confluent cells at 60 h. Difference spectra showed that the largest differences were observed between confluent cells and cells in early growth stages. Differences may reflect cell morphological changes, biochemical activity, and degree of ATR crystal exposure to the bulk medium. ATR/FT-IR spectroscopy of living Chinese hamster ovary cells was also used in a toxicological study to monitor the effects of hydroxyurea, an inhibitor of DNA synthesis. Delayed growth was observed in the cell growth curve of the hydroxyurea-treated cells during the course of treatment as compared to the control culture.

Animals

Seroprevalence of human immunodeficiency virus among childbearing women. Estimation by testing samples of blood from newborns.

Attempts to predict the course of the epidemic of acquired immunodeficiency syndrome (AIDS) have been hampered by the lack of an objective, practical way to estimate the prevalence of infection with the human immunodeficiency virus (HIV) in the general population. Testing for the prevalence of HIV infection in women should be a sensitive means to track the epidemic and to study the potential for perinatal transmission. Antibodies in maternal blood are contained in neonatal blood specimens routinely collected on absorbent paper for other purposes, such as screening for phenylketonuria; we therefore tested for HIV antibody in these specimens. Analysis of batches of individually blinded specimens from selected hospitals protected the anonymity of the mothers and babies and was cost efficient. Using the newborn's blood as an indicator of the mother's serologic status, we concluded that 1 of every 476 women (2.1 per 1000) giving birth in Massachusetts was positive for HIV antibody by immunofluorescence assay or enzyme-linked immunosorbent assay, both confirmed by immunoblot (Western blot) testing. The prevalence of HIV infection varied according to the type and location of the maternity hospitals; rates of seropositivity were highest in inner-city hospitals (8.0 per 1000), lower in mixed urban and suburban hospitals (2.5 per 1000), and lowest in suburban and rural hospitals (0.9 per 1000). This method is useful for collecting data needed to plan and evaluate prevention strategies and to predict the health care resources that will be needed to care for women and children who contract AIDS. Because other states have newborn screening programs similar to the Massachusetts program, this approach can be used for national surveillance of AIDS in women.

Acquired Immunodeficiency Syndrome