Neonatal Bartter's syndrome with hyperkalemia and normal urinary prostaglandin E2.
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Biomedical subjects
Publications and source records attributed to A H Klein.
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Results of a national survey of the current use of steroids in newborns in 1993 showed that 95% of the neonatologists in the United States have used dexamethasone for neonates at risk for chronic lung disease. Dexamethasone therapy for a period of a week or longer is associated with suppression of the hypothalamic-pituitary-adrenal axis (HPAA) in a substantial number of premature infants. A review of our current understanding of the biochemical tests evaluating HPAA function in premature infants and suggested guidelines for HPAA evaluation and management following dexamethasone therapy are presented.
The Bankart lesion of the shoulder has long been associated with anterior instability. Our laboratory has developed a biomechanical model of the human shoulder which was used to determine the effects of creating a Bankart lesion on cadaveric specimens and then to compare the effects of two repair techniques. The model simulates the abducted, externally rotated position of the glenohumeral joint and uses pneumatic cylinders to simulate the rotator cuff forces. Specimens were tested intact following a partial Bankart lesion, following a complete Bankart lesion, and after performing a Bankart repair using three Mitek suture anchors. Finally, both the traditional and Mitek repairs were tested until failure. Strain in the inferior glenohumeral ligament (IGHL) and torque resistance was measured as an indication of instability of the joint. Strain was noted to decrease with increasing depth of lesion of the IGHL. Torsional rigidity of the shoulder decreased with increasing depth of lesion as well. Repairing the shoulder restores the strain and rigidity to control conditions. The mean load until failure was greater with the traditional repair than with the suture anchor technique. This study quantitates the effects of a Bankart lesion of the shoulder, and demonstrates that repairing the lesion with a suture anchor technique restores the biomechanics of the shoulder.
In 21 revision total hip arthroplasties (THA), a 2-5-cm window was cut into the anterolateral cortex of the femur, and the cement distal to the window was removed under direct vision. In each case, a cemented THA was revised to a noncemented implant that bypassed the window by at least two femur diameters. The section of cortical bone was replaced; autogeneic bone graft was applied to the osteotomy site, and cerclage wires were used to hold the window in place. Postoperatively, all patients were maintained at partial weight-bearing (touchdown) for six weeks and then advanced as they were able. The mean follow-up time in this series was 22 months. Access to the femoral cement was greatly facilitated by the use of a femoral window. There were no intraoperative femoral fractures or inadvertent femoral perforations during cement removal. The mean healing time for the windows was 17 weeks. There was no association of femoral thigh pain or implant loosening with femoral windows. The windows heal rapidly and have not been associated with perioperative femoral fractures.
Impingement syndrome is an ill-defined term for a variety of disorders of the shoulder that manifest as anterior shoulder pain, especially during overhead activities. These disorders each have a common pathologic course that includes rotator cuff tendinitis (RCT), and, if untreated, may proceed to cuff rupture. RCT has at least two distinct etiologies. Primary impingement of the supraspinatus tendon on the coracoacromial arch is responsible in the majority of nonathletic cases. Overhead movements in sports are prone to developing secondary mechanical impingement because of an instability pattern that is common in this population. Information from this review and clinical practice permits differentiation of the two distinct etiologies of RCT which is important in treatment planning. Much work still needs to be done in defining the microscopic pathology of RCT.
The effect of dexamethasone therapy on hypothalamic-pituitary-adrenal axis function was prospectively investigated in very low birth weight infants with bronchopulmonary dysplasia. Ten infants (mean +/- SD birth weight 825 +/- 265 g, gestation 25.8 +/- 1.9 weeks, postnatal age 33.1 +/- 17.7 days) initially received intravenous dexamethasone, 0.5 mg/kg per day for 3 days, and then were weaned over a period of 45 +/- 19.0 days to a replacement dose, followed by a metyrapone test. Morning plasma cortisol and 11-deoxycortisol levels were measured before and after an oral metyrapone dose given at midnight. Five infants (group A: birth weight 876 +/- 313 g, gestation 26.2 +/- 1.3 weeks, age of entry 31.8 +/- 22.8 days) had normal metyrapone test results, and five infants (group B: 778 +/- 234 g, 25.4 +/- 2.5 weeks, 34.4 +/- 13.4 days) had suppressed test results. Group A infants, in comparison with group B infants, had higher basal cortisol plasma levels (14.52 +/- 12.53 and 3.00 +/- 1.38 micrograms/dL, P = .047), higher postmetyrapone 11-deoxycortisol plasma levels (3.11 +/- 3.93 and 0.55 +/- 0.51 micrograms/dL, P = .028), larger differences between basal and postmetyrapone cortisol levels (7.10 +/- 4.67 and 2.12 +/- 1.31 micrograms/dL, P = .047), and larger differences between basal and postmetyrapone 11-deoxycortisol levels (2.99 +/- 3.93 and 0.29 +/- 0.25 micrograms/dL, P = .009). The hypothalamic-pituitary-adrenal axis function in group B infants eventually returned to normal when they continued to receive low-dose dexamethasone therapy after a period of 36.8 +/- 16.6 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen consumption and 3H-guanosine diphosphate (GDP) binding were determined in brown adipocytes and mitochondria from 28-day gestation fetuses of alloxan-diabetic rabbit does and saline-injected controls. Maternal diabetes was classified as severe or mild determined by whether maternal blood glucose values were greater or less than 200 mg/dL, respectively, at death. Basal oxygen consumption and adipocyte diameters did not vary among groups. A significant reduction in maximal norepinephrine (NE) stimulated O2 consumption by fetal brown adipose tissue (BAT) cells was seen in offspring of severely diabetic pregnancies when compared with control values (248 +/- 53 +/- v482 +/- 32 microL O2/10(6) cells/h; P less than .005). In contrast, a significant increase in maximal NE-stimulated O2 consumption by fetal BAT cells occurred in offspring of mild diabetic pregnancies (807 +/- 60, P less than .001 v controls). A highly significant inverse correlation between serum glucose levels and maximal O2 consumption by fetal BAT was observed in fetuses from mild and severe diabetic pregnancies (r = -.98, P less than .005), and there was no correlation between these two parameters in offspring of normal pregnancies. A significant inverse correlation was observed between maximal O2 consumption by fetal BAT cells and serum insulin levels in offspring of both control and diabetic pregnancy (r = -.74; P less than .02). Tissue cytochrome oxidase activity was lower in offspring of severely affected diabetic does, indicating a reduction in BAT mitochondrial content compared with controls. BAT mitochondria from fetuses of severely diabetic does exhibited reduced 3H-GDP capacity, which was 2.5-fold lower than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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The purpose of this study was to measure the strain on the brachial plexus that results from traction loads applied at various arm positions and to correlate this with visibility through the arthroscope. We mounted strain gauges to the upper trunk, lateral cord, median nerve, and radial nerve of five fresh human cadavers. Each cadaver was placed in a lateral decubitus position, with the head fixed in a neutral position, as for shoulder arthroscopy, and the strain on the plexus was measured as a function of arm position and traction load. A final cadaver was used to determine the accessibility and visibility in the arthroscope at each of the arm positions. At a given flexion angle, increasing abduction is associated with decreasing strain. At a given abduction angle, increasing flexion results in decreased strain. The minimum overall strain was noted at 90 degrees of flexion and 0 degree of abduction. Visibility at this position is limited. We conclude that the ideal arthroscopic position is a combination of two positions that would maximize visibility while minimizing strain to the nerves. These two positions are 45 degrees of forward flexion and 90 degrees of abduction in combination with 45 degrees of forward flexion and 0 degree of abduction.
We investigated the effect of the transient neonatal hyperthyroid state on thermogenesis at birth by measuring rectal temperature, plasma free fatty acids, plasma catecholamines, and in vitro brown adipose tissue respiration in thyroidectomized (n = 6) and sham operated (n = 5) fetal sheep. Surgery was performed at an average of 133 days of gestation followed by cesarean delivery at 146 days. Fetuses were delivered into a constant room temperature of 25 degrees C. Serial measurements were made in utero before delivery and at timed intervals after birth. Serum 3,3',5 triiodothyronine and thyroxine concentrations in the neonatal period were normal in sham operated and nondetectable in thyroidectomized fetuses. Rectal temperatures and serum free fatty acid levels were reduced in thyroidectomized newborns. Plasma epinephrine concentrations were increased and the hypothyroid neonates were acidotic when compared to control animals. In vitro basal and norepinephrine stimulated brown adipose tissue respiration were reduced in thyroidectomized compared to control animals. These results indicate that thyroid hormone deficiency impairs nonshivering thermogenesis in brown adipose tissue and leads to hypothermia despite augmented plasma epinephrine values.
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The effect of altered thyroid status on the development of beta-adrenergic receptor (BAR) density and affinity was investigated in ovine fetal and newborn heart and lung. Fetal (119-121 days gestation) and newborn (2-3 days of age) sheep underwent either thyroidectomy alone, thyroidectomy plus infusion of a large dose of T3 or sham operation. Eight days later BAR were measured in heart and lung using the tritiated radioligand dihydroalprenolol. There was no apparent effect of altered thyroid status on fetal heart or lung BAR density or affinity. In contrast, the newborns thyroidectomized and infused with T3 had a 96% increase in heart BAR density and an 83% increase in lung BAR compared to the thyroidectomized only or sham-operated newborns which were similar. These results suggest that in the near term ovine fetus heart and lung tissue BAR are neither dependent on nor responsive to thyroid hormones, whereas in the newborn period heart and lung BAR are highly responsive to thyroid hormones.
Using optimal tissue concentration, supplemented with a thiol-protecting agent, the fetal liver has lower T4 5'-monodeiodinating activity than maternal or neonatal tissue. This is a true deficiency and is not due to deficiency of sulfhydryl groups in fetal tissue as previously suggested. Evidence indicates a dissociation of the neonatal surge of serum T3 and the increase in hepatic T4 to T3 conversion activity, suggesting that the neonatal T3 surge is related more to thyroid gland stimulation than to T4 to T3 conversion in non-thyroid tissues.
The effects of exogenous changes in thyroid status on in vitro brown adipose tissue (BAT) cellular respiration and thermogenic enzymes (sodium-potassium ATP' ase and alpha-glycerophosphate dehydrogenase) were studied in fetal sheep. Thyroidectomy and insertion of a constant infusion pump followed by 8 days of infusion of either T3 (n = 7) or vehicle (n = 4) were performed in fetal lambs at 119-121 days gestation. The animals were then killed, and perirenal BAT was removed for study. T3 infusion resulted in a mean plasma T3 concentration of 322 +/- 52 ng/dl compared to levels at the limits of detection (9 ng/dl) in the vehicle-infused animals. Basal respiration values with or without ouabain were similar in the two groups. Maximum mean norepinephrine (NE; 10(-6) M)-stimulated respiration (110.2 +/- 11.6 microliter O2/10(6) cells X h) in the T3-treated group was greater than stimulated mean respiration (55.3 +/- 15.6 microliter O2/10(6) cells X h) in the untreated animals (P less than 0.02). NE-stimulated respiration in the presence of ouabain (i.e. nonsodium transport-dependent respiration) was increased in the T3-treated animals (P less than 0.01), while sodium transport-dependent respiration was not different. (Bu)2cAMP-stimulated respiration was greater in the T3-treated group (P less than 0.001), while alpha-glycerophosphate substrate respiration was not different. Mitochondrial alpha-glycerophosphate dehydrogenase and Na-K-ATPase activities were similar. These studies demonstrate that BAT catecholamine-stimulated respiration is influenced by thyroid status in the ovine fetus. The increase in both NE- and (Bu)2cAMP-stimulated respiration suggests a postreceptor effect on intracellular metabolism, though an effect on beta-adrenergic receptors also might have occurred. Neither sodium transport (NA-K-ATPase)-dependent respiration nor mitochondrial alpha-glycerophosphate dehydrogenase appear to be involved. These data suggest that the relative hyperthyroid state that occurs in the newborn of both man and sheep may be important through its effects on BAT metabolism to insure adequate temperature regulation during neonatal adaptation.
The effect of both exogenous and endogenous changes in thyroid status on in vitro tissue respiration and thermogenic enzymes (sodium-potassium-adenosine triphosphatase and alpha-glycerophosphate dehydrogenase) was studied in fetal and newborn sheep. Oxygen consumption of liver and brain increased from 25 +/- 4.1 and 58.5 +/- 2.8 microliters O2 X 100 mg-1 X h-1, respectively, in tissues from unthyroidectomized fetal animals at 136-140 days gestation to 60 +/- 4.2 and 72 +/- 1.5 microliters O2 X 100 mg-1 X h-1 in tissues from unthyroidectomized newborn lambs between birth and 7 days of age. The physiological changes in thyroid function that normally occur at birth resulted in a mean (+/- SE) plasma triiodothyronine (T3) concentration of 563 +/- 39 ng/dl in the newborn lambs compared with 39 +/- 8 ng/dl in the fetal animals. Kidney respiration and thermogenic enzyme activities in the several tissues studied did not change. Liver, kidney, and brain respiration and thermogenic enzymes from T3-treated thyroidectomized fetal and newborn lambs were not increased (compared with untreated thyroidectomized animals) despite a marked increase in plasma T3 concentrations. Conclusions are that 1) liver, kidney cortex, and frontal brain cortex in the fetal and newborn lamb are relatively insensitive to the calorigenic effect of thyroid hormones, and 2) a perinatal increase in hepatic and cerebral respiration occurs in newborn animals (compared with fetal animals) but is probably not due solely to perinatal increases in thyroid hormones.
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Despite the importance of brown adipose tissue (BAT) in the regulation of thermogenesis and energy expenditure in both newborn and adult mammals, the functional ontogenesis of this tissue is largely unknown. In the present study, we describe the maturation of several aspects of BAT thermogenesis in fetal and newborn sheep. Cell respiration of brown adipocytes isolated from perirenal BAT was measured using a Gilson differential respirometer. Cells were isolated from four fetal animals at 121-124 days gestation (group 1), five fetal animals at 137-140 days gestation (group 2), and five newborns between birth and 4 days of age (group 3). In addition to basal oxygen consumption, in vitro cell respiration also was measured after the addition of norepinephrine (NE), (Bu)2cAMP, alpha-glycerophosphate (alpha GP), and butyric acid. Mean (+/- SEM) basal respiration (in microliters of O2 per 10(6) cells/h) increased from 11 +/- 1 in group 1 to 31 +/- 2 in group 2 and 45 +/- 7 in group 3. Cell volume increased from 9 +/- 1 pl in group 1 to 13 +/- 2 pl in group 2 and 18 +/- 2 pl in group 3. After adjustment for variations in basal respiration due to differences in cell volume, basal respiration in group 2 was greater than that in group 1 and equal to that in group 3. Maximal NE (10(-6) M)-stimulated respiration increased from 74 +/- 16 in group 1 to 294 +/- 47 in group 2. Maximal NE-stimulated respiration in group 3 (133 +/- 30) was less than that in group 2, but equal to that in group 1. (Bu)2cAMP-stimulated respiration increased from 51 +/- 12 in group 1 to 175 +/- 22 in group II, with no further increase in group III. Neither NE- nor (Bu)2cAMP-stimulated respiration varied significantly with cell volume. alpha GP substrate respiration demonstrated significant increases from group 1 to group 2, with another significant increase in Group 3. Butyric acid substrate respiration in group 1 was less than those measured in groups 2 and 3, while respiration values in groups 2 and 3 were equal. After adjustments for variations due to differences in cell volume, the patterns of development of both alpha GP and butyric acid substrate respiration were unaltered. The following conclusions were reached 1) Full maturation of BAT catecholamine-stimulated cellular respiration occurs before delivery near term in the ovine fetus. 2) In the neonatal lamb, a decrease in catecholamine-stimulated respiration occurs without a decrease in (Bu)2cAMP-stimulated respiration. This suggests that a decrease in BAT sensitivity to NE occurs after delivery at the receptor adenyl cyclase level. 3) The perinatal increase in alpha GP substrate respiration without an increase in butyric acid substrate respiration suggests that mitochondrial alpha-glycerophosphate dehydrogenase activity is increased. This was confirmed by measuring increased alpha-glycerophosphate dehydrogenase activity in crude BAT mitochondrial fractions in group 3 animals.