Accuracy of surgery clerkship performance raters.
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Clinical Clerkship↗
Biomedical subjects
K D Anderson
Publications and source records attributed to K D Anderson.
Distribution and relative abundance of neurons in the pigeon forebrain containing somatostatin, neuropeptide Y, or both.
Immunohistochemical studies in several mammalian species and in red-eared turtles have shown that somatostatin (SS) and neuropeptide Y (NPY) co-occur in a substantial proportion of the telencephalic neurons containing either. To explore further the possibility that telencephalic neurons co-containing SS and NPY may be evolutionarily conserved among amniotes, we determined the distribution and co-occurrence of SS and NPY in forebrain neurons in pigeons. Single-label immunohistochemical studies revealed the presence of overlapping populations of SS+ neurons and NPY+ neurons in most of the major subdivisions of the telencephalon. Double-label immunofluorescence studies revealed that in subdivisions of the telencephalon that are comparable to mammalian cortex (i.e., those dorsal and lateral to the basal ganglia), the vast majority of NPY+ neurons were also SS+, whereas a major and regionally variable percentage of the SS+ neurons were not NPY+. In contrast, within the basal telencephalon (including the basal ganglia and several other structures) neurons labeled only for NPY or only SS were more abundant than those containing both neuropeptides. Outside the telencephalon, the only forebrain cell group containing neurons in which SS and NPY were co-localized was in the lateral hypothalamus. A series of double- and triple-label immunohistochemical studies was undertaken to determine the extent of co-occurrence of SS and NPY in striatal neurons and the relationship of these neurons to striatal neurons containing other neuropeptides. In addition, immunohistochemical single- and double-label techniques were employed in conjunction with retrograde-labeling by fluorogold to determine the projections of SS+ and NPY+ striatal neurons. The results indicate that: 1) a population of striatal interneurons containing both SS and NPY exists in pigeons and constitutes approximately the same fraction of all striatal neurons as reported in mammals, 2) neurons containing NPY (but not SS) form a second, larger population of striatal interneurons, 3) neurons containing SS (but not NPY) form a third population of striatal interneurons that is approximately half as abundant as the NPY+ interneuron population, and 4) one-third of the substance P-containing striatonigral projection neurons also contain SS. The existence in pigeons of a major population of neurons containing both SS and NPY throughout the telencephalon, the existence of a population of neurons containing only SS in cortex-equivalent parts of the telencephalon, and the existence of a population of interneurons containing only NPY in the striatum is consistent with findings in mammals and turtles.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A controlled trial of corticosteroids in children with corrosive injury of the esophagus.
BACKGROUND: It is controversial whether treatment with corticosteroids reduces stricture formation in the esophagus after the ingestion of caustic material. METHODS: We conducted a prospective study over an 18-year period in which 60 children (median age, 2 years) with esophageal injury from the ingestion of caustic material were assigned randomly to treatment either with or without corticosteroids. The corticosteroids were given initially as prednisolon (2 mg per kilogram of body weight per day intravenously) and then as prednisone orally to complete a three-week course. All patients were evaluated by esophagoscopy within 24 hours of the ingestion. Those with moderate or severe esophageal injury had repeat esophagoscopy and barium swallow at follow-up. RESULTS: Esophageal strictures developed in 10 of the 31 children treated with corticosteroids and in 11 of the 29 controls (P not significant). Four children in the steroid group and seven in the control group eventually required esophageal replacement (P not significant). All but 1 of the 21 children with strictures had severe circumferential burns on initial esophagoscopy. CONCLUSIONS: There appears to be no benefit from the use of steroids to treat children who have ingested a caustic substance. The development of esophageal stricture was related only to the severity of the corrosive injury.
Administration, Oral↗
Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization.
A number of different neuroactive substances have been found in striatal projection neurons and in fibers and terminals in their target areas, including substance P (SP), enkephalin (ENK), and dynorphin (DYN). In a preliminary report on birds and reptiles, we have suggested that SP and DYN are to a large extent found in the same striatal projection neurons and that ENK is found in a separate population of striatal projection neurons. In the present study, we have examined this issue in more detail in pigeons and turtles. Further, we have also explored this issue in rats to determine whether this is a phylogenetically conserved feature of basal ganglia organization. Simultaneous immunofluorescence double-labeling procedures were employed to explore the colocalization of SP and DYN, SP and ENK, and ENK and DYN in striatal neurons and in striatal, nigral, and pallidal fibers in pigeons, turtles, and rats. To guard against possible cross-reactivity of DYN and ENK antisera with each others' antigens, separate double-label studies were carried out with several different antisera that were specific for DYN peptides (e.g., dynorphin A 1-17, dynorphin B, leumorphin) or ENK peptides (leucine-enkephalin, metenkephalin-arg6-gly7-leu8, methionine-enkephalin-arg6-phe7). The results showed that SP and DYN co-occur extensively in specific populations of striatal projection neurons, whereas ENK typically is present in different populations of striatal projection neurons. In pigeons, 95-99% of all striatal neurons containing DYN were found to contain SP and vice versa. In contrast, only 1-3% of the SP+ striatal neurons and no DYN neurons contained ENK. Similarly, in turtles, greater than 75% of the SP+ neurons were DYN+ and vice versa, whereas ENK was observed in fewer than 5% of the SP+ neurons and 2% of the DYN+ neurons. Finally, in rats, more than 70% of the SP+ neurons contained DYN and vice versa, but ENK was found in only 5% of the SP+ neurons and in none of the DYN+ perikarya. Fiber double-labeling in the striatum and its target areas (the pallidum and substantia nigra) was also consonant with these observations in pigeons, turtles, and rats. These results, in conjunction with studies in cats by M.-J. Besson, A.M. Graybiel, and B. Quinn (1986; Soc Neurosci. Abs. 12:876) strongly indicate that the co-occurrence of SP and DYN in large numbers of striatonigral and striatopallidal projection neurons in a phylogenetically widespread, and therefore evolutionarily conserved, feature of basal ganglia organization.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington's disease.
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Adult↗
Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia.
Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.
Adult↗
Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: should any infant be excluded?
Mortality in infants with congenital diaphragmatic hernia (CDH) remains high despite improvements in neonatal and surgical care because many infants develop persistent pulmonary hypertension of the newborn (PPHN) following repair. Since 1984, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in all infants (n = 25) with PPHN following CDH repair when conventional management failed, with an overall survival of 60%. Repair was performed in this hospital on 12 infants and in other hospitals in 13 infants transferred for consideration of ECMO after repair. Mortality was the same in the group repaired here and those transferred for ECMO. Although complications were frequent in the surviving group, they were successfully managed with nonoperative or operative therapy. Selective use of ECMO has been advocated in CDH patients based on various predictors of high mortality such as "best" PO2 postrepair less than 100 mm Hg, oxygenation index greater than 40, and ventilation index greater than 1,000 with PCO2 greater than 40. Seven surviving infants following ECMO would have been classified as unsalvageable by at least one parameter if selection criteria based on these parameters had been used. We conclude from this series that current predictors of high mortality in CDH patients are unreliable when ECMO is used. Surgeons caring for infants with CDH should consider the use of ECMO in all infants.
Extracorporeal Membrane Oxygenation↗
Extracorporeal membrane oxygenation therapy in neonates with septic shock.
Neonatal septic shock has significant morbidity and mortality with current therapeutic measures. At Children's National Medical Center, from June 1984 to October 1986, 10 of 100 patients treated with venoarterial extracorporeal membrane oxygenation (ECMO) had a documented diagnosis of septic shock. All of these infants fulfilled criteria consistent with 80% mortality using conventional intensive medical management. However, the survival rate for the septic neonates in this study was 100%. Compared with other groups of infants treated with ECMO, these septic neonates required significantly more ventilatory support after ECMO and had a higher incidence of chronic lung disease (30% v 12%). The septic neonates were also at higher risk for intracranial hemorrhage than the other infants treated with ECMO (40% v 26%). The necessity for prolonged intubation after ECMO for patients with septic shock suggests that this condition may be associated with additional structural damage not seen with meconium aspiration syndrome or respiratory distress syndrome. Nevertheless, for neonatal patients with septic shock unresponsive to conventional medical management, ECMO must be considered a viable alternative treatment.
Cerebral Hemorrhage↗
Patterns of injury in children.
Trauma is the leading cause of death for children over 1 year of age. This study was undertaken to identify the patterns of injury among children admitted to a regional pediatric trauma center. During a 34-month period, 3,472 injured children were consecutively admitted to a regional pediatric trauma center. Data were collected on medical, etiological, and financial aspects of injury. Eight subgroups were defined by mechanism of injury: motor-vehicle crash occupants, pedestrian and cycle injuries, falls, child abuse, gunshot and stab wounds, burns, poisonings, and foreign body ingestions or aspirations. Analysis of variance, Duncan's multiple range test, and contingency table analysis were used to determine differences among subgroups of children. Blunt and penetrating trauma accounted for 64.3% of all admissions. The mean age of injured children was 5.5 years; 64% of the children were boys. Sixty-seven percent of the children were admitted directly from the scene of injury. One-way analysis of variance yielded significant differences in mean age, mean hospital length of stay (LOS), mean intensive care LOS, mean trauma score, mean injury severity, and mean hospital charges by mechanism of injury (P less than .01). The overall mortality rate was 2.4%. Child abuse, gunshot/stab wounds, and drowning had the highest mortality rates, but injuries to motor-vehicle crash occupants and pedestrians accounted for the greatest number of deaths.
Accidental Falls↗
Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia.
To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed.
Evaluation Studies as Topic↗
A genetic therapy for familial hypercholesterolemia.
The WHHL rabbit serves as an animal model for the human genetic disease, familial hypercholesterolemia. In initial studies aimed at the development of a genetic therapy for familial hypercholesterolemia (i.e., introduction of a normal LDL receptor gene), WHHL rabbit skin fibroblasts were transduced with a retroviral vector expressing a normal human LDL receptor. Correction of the WHHL rabbit genetic defect in vitro was confirmed. Autologous fibroblasts expressing LDL receptors were reimplanted in donor rabbits and were found to survive and express the recombinant receptor in vivo for up to 4 weeks. In vivo LDL receptor expression by autologous cells stably transduced with functioning LDL receptors is possible. Transduction of greater numbers of cells along with increased cell survival in vivo may eventually lead to a specific and effective genetic therapy for familial hypercholesterolemia.
Animals↗
Gene expression in implanted rat hepatocytes following retroviral-mediated gene transfer.
An hepatocyte transplantation-gene transfer protocol has been developed whereby liver cells containing an expressing NeoR gene can be successfully implanted in vivo. Adult primary cultures of rat hepatocytes, after infection with the retroviral vector N2, were grown on a floating solid support (coated with purified collagen IV) in a serum-free hormonally defined medium designed for hepatocytes that also contained G418. Under these conditions, normal adult hepatocytes expressing the NeoR gene could be grown to high density. The solid supports holding the gene-engineered hepatocytes were then implanted into adult rats into subcutaneous and intraperitoneal sites. After one to two weeks, the supports were removed and shown to still contain the gene-engineered hepatocytes expressing the NeoR gene. These results suggest that cells from solid organs, such as the liver, are potential targets for gene transfer and expression studies in vivo.
Animals↗
Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.
One of the promises of modern molecular biology has been the opportunity to use genetically modified human cells in a patient to permanently restore inborn errors of metabolism. Although it has been possible to introduce genes into mammalian cells and to control their expression, it has proven difficult to introduce mammalian cells as carriers of the modified genetic information into hosts. The successful implantation of selective cells cannot be achieved without adequate vascular support, an essential step toward integration and reconstitution of a new biological function. Although a partial solution to this problem has been found by inducing specific site-directed neovessel formation using heparin-binding growth factor 1 (HBGF-1) adsorbed to a collagen matrix, these implants function for only a short period (weeks). We now report the formation of organoid neovascular structures using polytetrafluoroethylene fibers coated with collagen and HBGF-1 implanted in the peritoneal cavity of the rat. The organoid structures contained readily visible vascular lumina and nonvascular structures that resemble nerve tissue. It was also possible to demonstrate that the vascular system on the implant is continuous with the vascular tree of the host. This feature was used to demonstrate that the organoid structures are capable of sustaining the biological function of implanted normal rat hepatocytes over long periods of time (months) in the homozygous Gunn rat, thereby facilitating future applications involving the delivery of new genetic information.
Animals↗
Current results in repair of esophageal atresia with tracheoesophageal fistula using physiologic status as a guide to therapy.
Since 1966, 118 infants with esophageal atresia associated with tracheoesophageal atresia (Vogt-Gross Type C) have been operated upon with an overall survival rate of 90% at our institution. Since Haight's first survivor in 1941, argument has continued about the relative merits of immediate repair, delayed primary repair, and staged repair, and the criteria for selection of each approach. The Waterston classification served as the foundation for selection of surgical management from 1966 to 1982. Since 1982, physiologic status has been used as the sole basis for surgical management without regard to weight, gestation, or pulmonary condition. Twenty-six patients so chosen for immediate repair have all survived. Fewer have required gastrostomy, and the average hospital stay has shown significant decrease, a reflection of improved overall care of the neonate. Thirteen infants with severe cardiopulmonary compromise had some form of staged repair in this latter period with a 77% survival rate. Our experience using a refinement of Waterston's principles has led to more and earlier primary repairs with maintenance of excellent survival rates in stable infants. A staged approach is still useful for certain severely compromised infants.
Birth Weight↗
Site-directed neovessel formation in vivo.
Angiogenesis is an important component of organogenesis and wound repair and occurs during the pathology of oncogenesis, atherogenesis, and other disease processes. Thus, it is important to understand the physiological mechanisms that control neovascularization, especially with methods that permit the molecular dissection of the phenomenon in vivo. Heparin-binding growth factor-1 was shown to bind to collagen type I and type IV. When complexed with gelatin, heparin-binding growth factor-1 can induce neovascularization at polypeptide concentrations that are consistent with the biological activity of the mitogen in vitro. The adsorption strategy induces rapid blood vessel formation at and between organ- and tissue-specific sites and permits recovery of the site-specific implant for examination and manipulation by molecular methods.
Animals↗
Differential loss of striatal projection neurons in Huntington disease.
Huntington disease (HD) is characterized by the loss of striatal projection neurons, which constitute the vast majority of striatal neurons. To determine whether there is differential loss among different populations of striatal projection neurons, the integrity of the axon terminal plexuses arising from the different populations of substance P-containing and enkephalin-containing striatal projection neurons was studied in striatal target areas by immunohistochemistry. Analysis of 17 HD specimens indicated that in early and middle stages of HD, enkephalin-containing neurons projecting to the external segment of the globus pallidus were much more affected than substance P-containing neurons projecting to the internal pallidal segment. Furthermore, substance P-containing neurons projecting to the substantia nigra pars reticulata were more affected than those projecting to the substantia nigra pars compacta. At the most advanced stages of the disease, projections to all striatal target areas were depleted, with the exception of some apparent sparing of the striatal projection to the substantia nigra pars compacta. These findings may explain some of the clinical manifestations and pharmacology of HD. They also may aid in identifying the neural defect underlying HD and provide additional data with which to evaluate current models of HD pathogenesis.
Adolescent↗
Effects of melatonin and 6-methoxybenzoxazolinone on photoperiodic control of testis size in adult male golden hamsters.
Consumption of young plants containing 6-methoxybenzoxazolinone (6-MBOA) appears to play an important role in the initiation of reproduction each spring in wild populations of the montane vole. Following its identification, 6-MBOA has been found to stimulate the reproductive system in a number of rodent species, but the mechanism of action remains unknown. The chemical structure of 6-MBOA is similar to melatonin, which, in addition to its well-known antigonadal effects, can exert a progonadal influence under certain experimental conditions. To determine if 6-MBOA might act as a melatonin agonist, four experiments were conducted to compare the effect of these two compounds on testis size in the golden hamster, a rodent whose responses to melatonin are well characterized. 1) Hamsters exposed to 14 h light per day (14L:10D) received a daily injection of melatonin (25.0 micrograms) or 6-MBOA (17.8 micrograms). 2) Hamsters exposed to 6L:18D received Silastic capsules (50 or 200 mm) containing melatonin or 6-MBOA. 3) Hamsters exposed to 6L:18D received chow containing melatonin (21.1 or 42.2 micrograms/gm chow) or 6-MBOA (15.0 or 30.0 micrograms/gm). 4) Hamsters exposed to 6L:18D received drinking water containing melatonin (15.5 micrograms/ml) or 6-MBOA (11.0 micrograms/ml). Testis widths were determined at 2--3 week intervals, and after 66-73 days testes were removed and weighed. Melatonin significantly influenced testis size in each experiment, but treatment with 6-MBOA had no effect in any of these experimental paradigms, indicating that 6-MBOA does not act as a melatonin agonist in the hamster. However, these results indicate that the consumption of melatonin (and presumably melatonin agonists) could serve as an environmental stimulus for reproductive activity.
Animals↗
Extracorporeal membrane oxygenation in the management of respiratory failure in the newborn.
The history of ECMO and the development of its present-day use is discussed. The results of the National ECMO Registry and the first 100 patients at Children's Hospital National Medical Center are presented. Future developments and directions of ECMO are presented.
Extracorporeal Circulation↗