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Biomedical subjects

M L Walker

Publications and source records attributed to M L Walker.

At least 73 records · Page 4Linked to original sources
PubMed1990

Modulation of adrenocorticotropin-stimulated baboon fetal adrenal dehydroepiandrosterone formation in vitro by estrogen at mid- and late gestation.

We have reported that ACTH stimulation of dehydroepiandrosterone (DHA) formation by the baboon fetal adrenal at midgestation was suppressed by estrogen. Because fetal adrenal regulation changes with advancing gestation, the action of estrogen on fetal adrenal steroidogenesis may also be dependent on the degree of fetal adrenal maturation. We examined this possibility in the present study by determining the effects of ACTH and estrogen on DHA formation by adrenal cells of fetuses obtained from baboons at mid- and late gestation and from animals administered the antiestrogen MER-25 throughout late gestation. Because low density lipoprotein (LDL) provides substrate for the fetal adrenal, we also determined whether the effect of estrogen was mediated by LDL uptake. Adrenals were removed from baboon fetuses on day 100 (midgestation; n = 7) and day 170 (late gestation; n = 6; term, day 184) of gestation from untreated animals and on day 170 from fetuses whose mothers were treated with MER-25 on days 140-170 (25 mg/kg BW.day; n = 7). Cells were dispersed with 0.2% collagenase and incubated at 37 C for 3 h in 4 ml medium 199 with 10 nM ACTH, 10(-6) M estradiol and/or 500 micrograms LDL. The secretion of DHA into medium was determined by RIA. At midgestation, mean (+/- SE) basal DHA formation (nanograms per 10(5) cells/3 h) was 5.8 +/- 2.1, and DHA was increased (P less than 0.01) by ACTH to 20.0 +/- 5.9. Although estradiol alone had no effect, estradiol prevented the increase in DHA obtained with ACTH. Basal DHA production by adrenals of late gestation (0.7 +/- 0.3 ng/10(5) cells) was lower (P less than 0.01) than at midgestation. ACTH increased (P less than 0.01) DHA in a comparable manner near term in the presence (2.0 +/- 0.4) or absence (1.7 +/- 0.4) of estradiol. Thus, in contrast to day 100, estrogen did not attenuate the action of ACTH on adrenal cells on day 170. In fetal adrenal cells obtained on day 170 from MER-25-treated baboons, DHA formation (1.4 +/- 0.6 ng/10(5) cells) was comparably increased (P less than 0.05) to 2.4 +/- 0.2 and 3.0 +/- 0.5 ng/10(5) cells by ACTH in the absence or presence of estradiol. Thus, ACTH remained effective in enhancing DHA by adrenal cells of fetuses exposed in utero to antiestrogen. DHA formation by adrenals of midgestation was increased (P less than 0.05) to 15.4 +/- 4.8 and 27.4 +/- 7.5 ng/10(5) cells, respectively, by LDL and ACTH plus LDL.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1990

Principles of management of shotgun wounds.

As an instrument of close range combat, the shotgun has no parallel. At short distances, its destructive capacity parallels that seen from high velocity missile injury. In this study, the history of the shotgun, wound ballistics, principles of initial therapy and special management problems related to shotgun wounds of specific sites are reviewed. An analysis of pooled data on abdominal shotgun wounds is presented. A subset of patients who do not require abdominal exploration exists. Specific problems encountered in defining this subset are enumerated. Three algorithms are presented that summarize our current management approach to shotgun wounds of the torso and extremities.

Abdominal Injuries↗
PubMed1989

Light scattering and photocrosslinking in the calf lens crystallins gamma-II, III and IV.

The calf lens proteins gamma-II, -III and -IV crystallin have been photolyzed in pH 7.5 phosphate buffer solution at 25 degrees C. The photolysis light source was either a xenon arc lamp/monochromator system set to pass 290 +/- 5 nm or a nitrogen laser operating at 337.1 nm. Photolysis experiments at 337.1 nm were done both in the presence and absence of added 1.0 x 10(-4) M N-formylkynurenine (NFK). In addition, 1 x 10(-5) M riboflavin was added as a photosensitizer in a few of the experiments. All solutions were 1.0 mg ml-1 protein, and 1.0 ml of solution was irradiated for periods ranging from 10 min to 3 hr. During the 337.1 nm irradiations, the turbidity of the protein solutions was continuously monitored using a He-Ne laser at 632.8 nm. Progress of the 290 nm irradiations was monitored by observing the loss of tryptophan fluorescence for each of the gamma crystallin proteins. The rate of growth of light scattering, upon 337.1 nm irradiation, was greatest for gamma-IV. Addition of NFK caused the rates of growth of UV-induced light scattering of all three gamma crystallins to increase significantly. These rates were in the order: gamma-IV much greater than gamma-III greater than gamma-II. Following UV exposure, the protein solutions were analyzed using UV-visible absorption spectroscopy and SDS-PAGE. Irradiated gamma crystallin solutions showed increased optical density throughout the visible region, resulting from solution turbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

UV laser photodamage to whole lenses.

Lenses from rat or calf were exposed in vitro to UV radiation from a nitrogen laser operated at 337.1 nm or from an excimer laser operated at 3.8 nm. Visible light transmission was monitored during calf lens irradiations at 308 nm and found to decrease. Proteins were extracted from the irradiated rat or calf lenses, separated into water soluble and insoluble fractions, and analysed using SDS-PAGE. Comparison of these gels with dark controls showed that, following photolysis, there was loss of polypeptide material in the 20-30 kDa region and concomitant formation of polymers at 40 and 60 kDa, and at greater than 100 kDa in calf lens (308 nm irradiation) and rat lenses (337.1 nm irradiation) in vitro. In addition, there was evidence for formation of lower molecular weight polypeptides at 10 kDa in the protein from irradiated rat lenses. The rat SDS-PAGE gels were challenged against anti-calf gamma crystallin serum. There was clear evidence that the polymeric material, in the water insoluble protein fraction from the 337.1 nm photolyzed rat lenses was derived in part from gamma crystallin. The macromolecular changes detected in these photolyzed rat and calf lens proteins were similar to those previously reported to accompany aging in the human lens. Biochemical changes of the type observed in UV irradiated rat and calf lenses may be responsible for the loss of visible light transmission seen in calf lenses.

Animals↗
PubMed1989

Intrasession and intersession reliability of hand-held dynamometer measurements taken on brain-damaged patients.

Recent reports have characterized force measurements obtained with hand-held dynamometers from brain-damaged patients as being highly reliable. The purposes of this two-part study were to replicate essential parts of those studies and to further examine the reliability of these measurements in a clinical context. Repeated force measurements were taken from the nonparetic and paretic limbs of brain-damaged patients during the same testing session (Part 1) and during two testing sessions separated by two days (Part 2). The intratester intraclass correlation coefficients (ICCs) for all measurements taken during a single session ranged from .88 to .98. The ICCs for repeated measurements taken two days apart from the paretic limbs ranged from .90 to .98. The ICCs for repeated measurements taken two days apart from the nonparetic limbs ranged from .31 to .93. The ICCs for repeated measurements taken two days apart from the combined data for all limbs ranged from .79 to .97. Hand-held dynamometer measurements taken on brain-damaged patients appear to be highly reliable when taken during the same testing session. When repeated measurements are separated by a longer time interval, the measurements taken from the paretic limbs continue to be highly reliable, whereas most measurements taken on the nonparetic limbs exhibit poor reliability.

Adult↗
PubMed1989

Stereotactic surgery in children.

Stereotactic biopsy has been popularized over the last decade since the advent of newer, more sophisticated instrumentation and technology. However, less than 300 cases of pediatric stereotaxy are recorded in the literature and few reports emphasize the necessary modifications required in children. Sixty-six stereotaxic procedures were performed on 62 children using the Brown-Roberts-Well (BRW) apparatus at our institutions. The mean age was 9.0 years (range 5 months to 18 years). The indication for the technique was diagnostic in 36 cases and therapeutic in 9 cases; location was a factor in 21 children with the lesion involving a 'deficit-prone' area of the brain. The BRW technique was applicable in 61 procedures (93%). Inability to enter cysts or biopsy of necrotic tissue and tumor capsule occurred in 5 cases. One patient had a transient increase in cerebral edema, for an overall complication rate of 2%. It appears that the BRW stereotactic technique is equally effective in children and adults and will no doubt play an ever increasing role in the future of pediatric neurosurgery.

Adolescent↗
PubMed1989

Management of posthemorrhagic hydrocephalus in the low-birth-weight preterm neonate.

Over a period of 34 months from 1987 to 1990 we inserted ventricular catheter reservoirs (VCR) into 20 premature low-birth-weight infants who had developed progressive, symptomatic posthemorrhagic hydrocephalus following grade III or IV intraventricular hemorrhages. The mean estimated gestational age was 27.7 +/- 5.3 weeks and mean birth weight was 1,041 +/- 699 g. The ventricular catheter reservoirs were placed on day of life 30.7 +/- 29.7 and tapped for a total of 3-34 days at varying frequencies and for varying volumes. Of the 20 patients, 4 died on days of life 25, 76, 88, and 187. There were two reservoir infections, both occurring in infants who eventually died. The 16 survivors have been followed from 2 to 24 months (adjusted age). Four (25%) remain shunt-free and 3 have undergone VCR removal. There have been two shunt infections in the 12 shunted patients; ten shunt revisions have been performed overall. At the time of last follow-up, 14 patients were old enough to undergo neurodevelopmental evaluation. Five patients (36%) were 'normal' on gross neurological screening examination, 5 (36%) had 'mild developmental delay' and 4 (28%) had 'significant developmental delay'. We feel these data support the continued use of ventricular catheter reservoirs in the management of posthemorrhagic hydrocephalus and offer hope that some of these patients might remain shunt-free and most will have a normal or mildly delayed neurodevelopmental outcome.

Brain Damage, Chronic↗
PubMed1988

Dietary influences on growth and sexual maturation in premenarchial rhesus monkeys.

The effect of a high-fat diet on growth, sexual maturation, and developmental changes in serum levels of estradiol (E2), growth hormone (GH), somatomedin-C (Sm-C), and insulin were examined in outdoor-housed premenarchial rhesus monkeys. From 16 to 32 months of age, females were fed either a high-fat diet (HFD, N = 5) with 31% calories from fat or a control diet (commercial laboratory chow, N = 10) with 12% of the calories from fat. Maintenance on a HFD did not accelerate physical growth, as all animals exhibited similar increments in body weight, crown-rump length, and weight/height ratios. In contrast, the HFD group exhibited an earlier onset of perineal swelling and menarche despite lower body weights during that time. Moreover, 80% of the HFD animals exhibited an early first ovulation (31-32 months of age) compared with 40% of control animals. These reproductive changes were associated with significant differences in the endocrine profiles of HFD animals. Fasting serum levels of insulin were significantly elevated within 2 months of diet treatment and remained elevated throughout the study period. Levels of Sm-C were elevated relative to those of controls after 3 months of diet treatment, but not thereafter. Serum GH increased after 6 months on the HFD and, overall, concentrations were higher in HFD animals. A significant rise in E2 was observed after only 45 days on the HFD treatment. These concentrations did not differ from 18 to 21 months of age but again were elevated at 27 months in the HFD females. Since these endocrine and physical changes associated with reproductive physiology occurred in the absence of enhanced growth, these data suggest that a high-fat diet may influence the rate of sexual maturation through changes in certain metabolic factors which may act on the developing neuroendocrine system.

Animals↗
PubMed1988

Reliability of isometric muscle testing of knee flexor and extensor muscles in patients with connective tissue disease.

This two-part study evaluated the reliability of inexpensive devices for isometric muscle testing on patients. First, the relationship between gauge readings of the devices and known weights was evaluated. Coefficients of determination and regression lines were used to determine the strength and nature of this relationship, which was determined to be linear. Second, intratester reliability for force measurements of isometric knee extension and flexion motions was determined for 30 patients with connective tissue diseases. Right knee extensor and flexor muscle forces were measured during two sessions. The measurements between sessions were compared for degree of agreement using intraclass correlation coefficients. Intraclass correlation coefficients ranged from .90 to .95 for knee flexor force measurements and from .75 to .85 for knee extensor force measurements. Based on the results of this study, this measuring device can be used reliably to measure knee extensor muscle force at 50 degrees and knee flexor muscle force at 30 and 70 degrees.

Adolescent↗
PubMed1988

Prolonged lactational infertility in adolescent rhesus monkeys.

The present study examined the effects of first pregnancy and nursing behavior on postpartum infertility in seasonally breeding rhesus monkeys to assess whether prolonged lactational infertility observed in adolescent mothers is due to a particular pattern of nursing or to decrements in body growth rates. After a successful first pregnancy, a significant percentage of the lactating adolescent mothers (57.1%; n = 8) failed to exhibit an ovulation with normal luteal phase during the subsequent breeding season. In contrast, the remaining lactating adolescents (42.9%, n = 6) and all of the adult mothers (100%, n = 6) exhibited ovulations with a normal luteal phase. Age alone was not the critical variable, since all nonlactating adolescents exhibited ovulations with normal luteal phase parameters in the subsequent breeding season. The luteal phase abnormalities exhibited by the subset of lactating adolescent females were characterized by an inadequate luteal phase (ILP) and by significantly lower serum levels of progesterone, estradiol, and bioactive luteinizing hormone. The occurrence of these ILP ovulations was associated with more frequent nursing bouts prior to ovulation and during the subsequent luteal phase. In contrast, nursing patterns for adult females who had ovulations with normal luteal phases were more similar to those of the infertile lactating adolescents exhibiting significantly longer and more frequent nursing bouts, suggesting that fully adult females may be less sensitive to the inhibitory aspects of a suckling stimulus. Differences in luteal phase function among lactating adolescents were not related to differential rates of ponderal or skeletal growth. A still-developing neuroendocrine system may thus render a significant proportion of adolescent females more sensitive to suckling-induced suppression of gonadotropin secretion.

Animals↗
PubMed1988

Regulation of baboon fetal adrenal androgen formation by pituitary peptides at mid- and late gestation.

A short term incubation of baboon fetal adrenal cells obtained at midgestation and near term was used to determine whether a change in the regulation of androgen formation occurs with advancing gestation. Adrenal glands were removed from baboon (Papio anubis) fetuses on day 100 (mid; n = 7) or day 170 (late; n = 5) of gestation, and cells were dispersed with 0.2% collagenase. Cells (10(5] were incubated at 37 C for 3 h in medium 199 in the presence or absence of 10 nM ACTH, 10 nM ovine PRL, 10 nM ovine GH, 50 nM hCG, or 50 nM human chorionic somatomammotropin. Dehydroepiandrosterone (DHA), DHA sulfate (DHAS), cortisol (F), and androstenedione concentrations were determined in the medium by RIA. At midgestation, ACTH, PRL, and GH elevated (P less than 0.05) DHA (168%, 169%, and 178%, respectively) and DHAS (142%, 210%, and 197%, respectively) formation. Near term, ACTH and PRL retained their ability to stimulate (P less than 0.05) DHA (307% and 220%, respectively), but not DHAS, synthesis. The fetal adrenal at late gestation, however, lost its ability to respond to treatment with GH. hCG and human chorionic somatomammotropin did not stimulate steroidogenesis at either time of gestation. F formation at midgestation was less (P less than 0.05) than that at term and not responsive to ACTH. ACTH stimulated (P less than 0.05) F secretion by 68% in fetal adrenal cells obtained near term. The secretion of androstenedione was not affected by any peptide treatment at either stage of gestation. These data indicate that the responsivity of the baboon fetal adrenal to various pituitary peptides is different at two developmentally distinct stages of gestation. We conclude, therefore, that the regulation of fetal adrenal steroidogenesis changes with advancing gestation.

Adrenal Glands↗
PubMed1988

Hemispherectomy and diaschisis: rapid improvement in cerebral functions after right hemispherectomy in a six year old child.

Neuroradiological, neurological, and neuropsychological studies before and after hemispherectomy for seizures of a six year old boy with left hemiplegia at birth revealed striking postoperative improvement. Seizures ceased and have not recurred. Preoperative EEC studies from seven months of age revealed increasing pathological involvement of the left as well as right hemisphere. Postoperatively, normal tracings over the left hemisphere documented marked and continuing improvement. In contrast to markedly subnormal preoperative WISC-R IQs, retest at 19 months postoperatively showed WISC-R IQs within the normal range, with similar improvement in other tests of cognitive, motor and sensory functions. The arrest and reversal of the preoperative pattern of increasing deterioration and disappearance of pathological involvement of left as well as right hemisphere functions following surgery is consistent with the disappearance of diaschisis as described by von Monakow in 1914, and has conceivably significant clinical as well as theoretical implications.

Journal Article↗
PubMed1987

Relationships between lumbar lordosis, pelvic tilt, and abdominal muscle performance.

The purpose of this study was to examine the relationships between measurements of lumbar lordosis, pelvic tilt, and abdominal muscle performance during normal standing. In addition, the reliability of the measurements used in this study was examined. Measurements of lumbar lordosis, pelvic tilt, and abdominal muscle performance were taken of 31 healthy adults aged 20 to 33 years. Each measurement was taken twice, and the measurements were shown to be reliable. The Spearman's rho correlation of the abdominal muscle performance measurements with pelvic tilt was .18 and with lordosis was .06. The Pearson product-moment correlation of lordosis with pelvic tilt was .32. The results indicate that lumbar lordosis, pelvic tilt, and abdominal muscle function during normal standing are not related. This study demonstrates the need for a reexamination of clinical practices based on assumed relationships of abdominal muscle performance, pelvic tilt, and lordosis.

Abdominal Muscles↗
PubMed1987

Changes in the pattern of androgen formation in vitro by the baboon fetal adrenal gland at mid- and late gestation.

In the present study, baboon fetal adrenal cells were obtained at mid- and late gestation and incubated for various intervals to determine simultaneously the effects of length of incubation and stage of development on the pattern of adrenal steroidogenesis. Cells were treated with adrenocorticotropic hormone (ACTH) from 0 to 48 h of incubation, and the concentrations of dehydroepiandrosterone (DHA), DHA-sulfate (DHAS), and androstenedione (delta 4A) were determined in the medium. The secretion of DHA and DHAS by untreated or ACTH-treated cells of midgestation increased linearly throughout the 48-h incubation period. In fetal adrenal incubates of late gestation, however, DHA and DHAS concentrations peaked at 3 h and declined thereafter, suggesting that the DHA secreted into the medium was further metabolized by this tissue. Baboon fetal adrenal cells formed similar amounts of DHAS and DHA at midgestation, but greater quantities of DHAS were formed at term. In fetal adrenal incubates of midgestation, DHA concentrations exceeded those of delta 4A by threefold, a relationship which was reversed at late gestation, probably due to the increase in the activity of 3 beta-hydroxy-steroid dehydrogenase with advancing gestation. Because the decline in DHA with time of incubation was also associated with a concomitant decrease in DHAS and no change in delta 4A, it does not appear that formation of these steroids account for the loss of DHA. We conclude that the pattern of androgen metabolism exhibited by fetal adrenal cells obtained at midgestation is different from that at term.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗