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K D Anderson

Publications and source records attributed to K D Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats.

An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington's disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.

Animals↗
PubMed1994

Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: evidence of persistent surfactant deficiency.

Infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) can have initial lung atelectasis which, in survivors, gradually improves over time. To test the hypothesis that these patients could benefit from surfactant therapy, infants with CDH (born at > 34 weeks' gestation) on ECMO received either four doses of modified bovine lung surfactant extract (beractant) (surfactant group, n = 9) or an equal volume of air (control group, n = 8). Tracheal aspirate surfactant protein-A (SP-A) concentrations were initially low, and then increased over time in both CDH groups (P = .0021); however, levels remained low when compared with those of infants on ECMO who had other diagnoses (P = .04). Lung compliance (CL), time to extubation, time on oxygen, and total no. of hospital days were not different between the two groups. Infants with CDH had persistently elevated right ventricular pressure (RVP) at cessation of bypass when compared with non-CDH infants on ECMO (RVP = 53.25 mm Hg +/- 19.52 in the CDH group, 32.90 +/- 10.63 in the non-CDH group; P = .0121). The findings suggest that the postnatal surfactant deficiency may be more persistent in CDH infants than in non-CDH infants on ECMO. However, CDH remains a multifactorial condition, with delayed improvement, because of persistence of pulmonary hypertension, difficulties with vascular remodeling, degree of lung hypoplasia, or compromised respiratory mechanics.

Airway Resistance↗
PubMed1994

Diamond flap anoplasty in infants and children with an intractable anal stricture.

After posterior sagittal anorectoplasty for imperforate anus a prolonged course of anal dilatations is necessary until the scar softens. Although rare, severe stricture after this procedure is difficult to resolve. Y-V plasty is not entirely satisfactory because the pedicle advanced into the anus has some tension, which tends to retract producing recurrent stricture. The authors performed a diamond-shaped island anoplasty in eight children with postoperative and strictures (one after an unsuccessful Y-V plasty), with prompt resolution of the stricture in five. The island flap anoplasty consists of a diamond-shaped flap of skin formed laterally, with complete separation of skin and subcutaneous attachments around the periphery of the flap. The skin island is supplied with blood from the deep tissue. An incision is made through the scarred anal ring and into the mucosa, a distance of half the length of the diamond, which is then advanced into the mucosal defect. The defect lateral to the advanced flap is sutured closed. The island of skin descends naturally into the anus, under no tension. The procedure can be performed simultaneously in the 3 o'clock and 9 o'clock positions, and can later be repeated anteriorly and posteriorly, although this has not been necessary. Two of the eight children have required no dilatation postoperatively, a distinct advantage in the 4-year-old patient. One segment in one child sloughed, resulting in repeat stricture that is responding to dilatation. The other seven children are doing well with their colostomies closed.

Anus, Imperforate↗
PubMed1994

A pre-embedding triple-label electron microscopic immunohistochemical method as applied to the study of multiple inputs to defined tegmental neurons.

For many neural regions it is of interest to know the identity of the target structures of two different types of inputs to that neural region. Such studies require use of a triple-label immunohistochemical method to differentially label the class of target structure and the two types of input so that they can be visualized at the electron microscopic (EM) level. We describe here a procedure for combining three different markers (diaminobenzidine, benzidine dihydrochloride, and silver-intensified immunogold) for triple-label EM immunohistochemical pre-embedding labeling. All three markers are distinct at the LM and EM levels. An example of this approach as applied to studying striatal input to the ventral tegmental area is presented and the advantages of this approach are discussed.

Animals↗
PubMed1993

Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases.

This study describes the effects of two major treatment options, splenectomy and/or bone marrow transplantation, on the natural history of the Wiskott-Aldrich (WAS) syndrome. The records of 62 patients with the WAS evaluated at the National Institutes of Health Clinical Center from 1966 to 1992 were reviewed. Nineteen patients were treated with bone marrow transplantation (BMT) and the results were largely dependent on the source of the graft. Twelve of 12 patients receiving HLA-matched sibling marrow achieved satisfactory immunologic and hematologic reconstitution. By contrast, only 2 of 7 patients receiving haploidentical, parental, or matched unrelated marrow survived more than 1 year after BMT. Thirty-nine patients who lacked suitable bone marrow donors early in their course underwent splenectomy for management of their thrombocytopenia; most received prophylactic antibiotics to minimize the risk of sepsis. Nearly all these patients achieved normal platelet counts and the rate of serious bleeding was reduced nearly sevenfold. Median survival in the untransplanted splenectomy group was 25 years, compared with less than 5 years in unsplenectomized patients. We conclude that HLA-matched sibling donor BMT is the treatment of choice for patients with WAS and that splenectomy and daily prophylactic antibiotics provide a significant survival advantage to those boys without a matched sibling donor. Splenectomy should probably be used in preference to unmatched BMT until results with alternative donor BMT significantly improve or gene therapy becomes available.

Adolescent↗
PubMed1993

Co-occurrence of gamma-aminobutyric acid, parvalbumin and the neurotensin-related neuropeptide LANT6 in pallidal, nigral and striatal neurons in pigeons and monkeys.

Immunohistochemical double-labeling techniques were used to examine the co-localization of the neurotransmitter gamma-aminobutyric acid (GABA), the calcium-binding protein parvalbumin and the neurotensin-related hexapeptide LANT6 in neurons of the striatum and its target areas in pigeons and monkeys. The studies revealed the existence of a population of striatal interneurons apparently containing all three of these substances in both monkeys and pigeons. The results also revealed that GABA and LANT6 were co-localized in numerous pallidal and nigral reticulata neurons that also contained parvalbumin in both species. Examination of diverse other cell groups in avian forebrain and midbrain revealed that parvalbumin and LANT6 were typically co-localized to GABAergic neurons. In light of the presence of pallidal, reticulata and striatal neurons containing these three substances in two widely divergent amniote groups such as pigeons and monkeys, it seems likely that: (1) comparable neuronal populations are present in other avian and mammalian species; and (2) these neuronal populations play a fundamental role in basal ganglia functions that requires these three substances.

Animals↗
PubMed1993

Congenital diaphragmatic hernia: long-term outcome in neonates treated with extracorporeal membrane oxygenation.

As more infants with congenital diaphragmatic hernia (CDH) survive with extracorporeal membrane oxygenation (ECMO), it seems prudent to detail the longterm outcome in these medically complex infants. Eighteen children with CDH-treated with postoperative ECMO were recruited for participation in this study. The mean duration of ECMO was 193 hours (range 82 to 493 hours), mean time to extubation after ECMO was 142 hours (range 34 to 312 hours), and median duration of hospitalization was 46 days (range 30 to 181 days). Of the 18 infants, 4 (22%) were discharged home requiring oxygen therapy. At follow-up the notable findings were a high incidence of gastroesophageal reflux and failure to thrive. At both 1 and 2 years of age, 50% of infants were at less than the 5th percentile for weight. At 1 and 2 years of age, 39% and 21%, respectively, were at less than the 5th percentile for weight/length ratio. A total of 16 children (89%) had clinical evidence of reflux, and 8 (44%) were discharged home on a regimen of nasogastric feedings. Reherniation occurred in 4 children (22%) and was more frequent when a patch was used. An electrocardiogram showed right ventricular hypertrophy in 6 (43%); oxygen saturation by pulse oximetry was > 95% in all children, and pulmonary artery pressure was estimated by Doppler echocardiography to be normal in 12 of 14 children examined. The neurodevelopmental outcome (Bayley Scales or Stanford-Binet scale) at 1 to 4 years of age was not dissimilar from that of other ECMO-treated children. Given the severity of illness in the neonatal period, the general health and development of children with CDH surviving after ECMO are good. Surprisingly few children have long-term respiratory complications related to pulmonary hypoplasia. Follow-up in the first few years should be aimed at aggressive nutritional intervention to prevent the growth failure that appears to be prevalent in these children.

Brain Diseases↗
PubMed1992

Administration of carbachol into the lateral ventricle and suprachiasmatic nucleus (SCN) produces dose-dependent phase shifts in the circadian rhythm of locomotor activity.

The cholinergic agonist, carbachol, induces phase-dependent shifts in the timing of the circadian rhythm of locomotor activity (CRLA). The effects of carbachol injections into the lateral ventricles of hamsters were compared between circadian times that produce phase delays vs. phase advances in the CRLA. The shape of the dose-response curves and the ED50 for carbachol injections were similar for the two injection times. The second experiment demonstrated the dose-dependence of phase advances produced by carbachol injections into the area of the suprachiasmatic nucleus. These results indicate that carbachol exerts similar dose-dependent actions for both phases advances and phase delays.

Acetylcholine↗
PubMed1992

Ultrastructural double-labeling demonstrates synaptic contacts between dopaminergic terminals and substance P-containing striatal neurons in pigeons.

Immunohistochemical studies in rats have demonstrated dopaminergic input onto medium spiny neurons of the striatum. Medium spiny neurons, however, are known to consist of two major neuropeptide-specific types, those containing substance P (SP) and those containing enkephalin. Although both of these types have been shown to receive dopaminergic input onto their perikarya and proximal dendrites, the extent to which both types also receive direct dopaminergic input onto distal dendritic shafts or onto dendritic spines is uncertain. In the present study, we used EM immunohistochemical double-label techniques to examine the synaptic organization of dopaminergic input onto SP+ striatal neurons. We examined the striatum of pigeons, in whom SP+ striatal neurons, including their dendritic shafts and spines, can be readily labeled. Antibodies against tyrosine hydroxylase (TH) were used to identify dopaminergic terminals, which were labeled using silver-intensified immunogold. The SP+ neurons were labeled immunohistochemically using diaminobenzidine. We found that dopaminergic terminals make appositions and form symmetric synapses with the perikarya, dendritic shafts and dendritic spines of SP+ neurons. Thus, nigral dopaminergic neurons provide a monosynaptic input onto SP+ striatal neurons in a manner similar to that described for dopaminergic input onto striatal medium spiny neurons in general.

Animals↗
PubMed1992

Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington's disease.

We have reported previously that striatal projection neurons are differentially affected in the course of Huntington's disease, and in a prior patient report we noted that differential loss of striatal projection neurons occurs also in patients with presymptomatic Huntington's disease. Striatal neurons projecting to the external segment of the globus pallidus or the substantia nigra show evident loss, whereas those projecting to the internal segment of the globus pallidus appear relatively spared at presymptomatic and early stages of symptomatic Huntington's disease. We now report similar findings in a second apparently presymptomatic Huntington's disease allele carrier.

Adult↗
PubMed1992

Solitary thyroid nodules in 71 children and adolescents.

Seventy-one children and adolescents with a solitary nodule of the thyroid gland were seen over a 27-year period and all had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, 55 of which showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Fourteen of the 55 cold nodules were malignant (25.5%) while no malignancies were present in warm or hot nodules. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to their clinical management as derived from our experience are presented.

Adolescent↗
PubMed1992

A strategy for resection of Wilms' tumor with vena cava or atrial extension.

Resection of a Wilms' tumor that extends into the vena cava or right atrium results in excellent survival when combined with adjuvant therapy. Preoperative identification of the presence of intravascular tumor thrombus and the level of vascular involvement is essential. It facilitates safe surgical resection, with cardiopulmonary bypass immediately available for retrohepatic and atrial tumors. Six patients with intracaval or intracardiac tumor thrombus were treated over a 5-year period with no perioperative deaths. Preoperative chemotherapy was useful in two patients with extensive tumors and pulmonary metastases. Our results using an integrated management plan suggest that an aggressive surgical approach is justified for this extensive variant of Wilms' tumor.

Algorithms↗
PubMed1992

Long-term follow-up of children with colon and gastric tube interposition for esophageal atresia.

BACKGROUND: There are two major methods of esophageal substitution for children born with long-gap esophageal atresia. This study was undertaken to see whether one method of substitution emerged as clearly superior to the other. METHODS: Twenty-four UK children who received a colon transposition for esophageal atresia were compared with 15 US children with esophageal atresia who received a gastric tube. The charts of all patients were reviewed. Follow-up data were obtained by questionnaire, and more than 80% of patients were personally evaluated at follow-up clinics. RESULTS: At follow-up US children were 3 1/2 to 18 1/2 years of age; UK children were 7 1/2 to 19 years of age. Most of the children fell at or below the 10th percentile for height and weight, reflecting the tendency for prematurity in infants with esophageal atresia. One half of the children needed to eat slowly and to avoid certain meats. Dysphagia was rare. Older children ate socially with their friends without embarrassment. Early complications were technical; there were few late complications, and no difference was apparent between the two groups. CONCLUSIONS: In subjects who were growing, no difference was noted between the two methods of substitution as far as nutrition, growth, patient acceptability, or complications, early or late. Both groups functioned well and appeared to improve with the passage of time.

Anastomosis, Surgical↗
PubMed1991

Immunohistochemical localization of DARPP-32 in striatal projection neurons and striatal interneurons: implications for the localization of D1-like dopamine receptors on different types of striatal neurons.

Immunohistochemical double-label techniques were used to study the localization of DARPP-32, a phosphoprotein that is enriched in neurons possessing members of the D1 subfamily of dopamine receptors, in several different types of striatal neurons in the rat basal ganglia. The vast majority (94.1%) of striatonigral projection neurons (the vast majority of which contain substance P), identified by retrograde labeling with fluorogold, were observed to contain DARPP-32. Similarly, the vast majority of striatopallidal projection neurons (87.7%), identified by immunofluorescence labeling for enkephalin (ENK), were found to label for DARPP-32. In contrast, cholinergic and neuropeptide Y-containing striatal interneurons were never observed to contain DARPP-32. These results suggest that essentially all major types of striatal medium spiny projection neurons may possess members of the D1 subfamily of dopamine receptors, but that striatal local circuit neurons do not possess members of the D1 subfamily of receptors.

Animals↗
PubMed1991

Ultrastructural single- and double-label immunohistochemical studies of substance P-containing terminals and dopaminergic neurons in the substantia nigra in pigeons.

The vast majority of striatonigral projection neurons in pigeons contain substance P (SP), and the vast majority of SP-containing fibers terminating in the substantia nigra arise from neurons in the striatum. To help clarify the role of striatonigral projection neurons, we conducted electron microscopic single- and double-label immunohistochemical studies of SP+ terminals and/or dopaminergic neurons (labeled with either anti-dopamine, DA, or anti-tyrosine hydroxylase, TH) in pigeons to determine: (1) the synaptic organization of SP+ terminals, (2) the synaptic organization of TH+ perikarya and/or dendrites, and (3) the synaptic relationship between SP+ terminals and TH+ neurons in the substantia nigra. Tissue single-labeled for SP revealed numerous SP+ terminals contacting thin unlabeled dendrites in the substantia nigra, but few SP+ terminals were observed contacting perikarya or large-diameter dendrites. SP+ terminals contained round, densely packed, clear vesicles, and often contained one or more dense-core vesicles. Synaptic junctions between SP+ terminals and their targets were more often symmetric (86%) than asymmetric. In tissue single-labeled for DA, we observed few terminals contacting DA+ perikarya, whereas terminals contacting DA+ dendrites were more abundant. Terminals contacting DA+ structures comprised at least four different morphologically distinct types based on the morphology of the clear synaptic vesicles and the type of synaptic junction. One type of terminal contained round clear vesicles and made symmetric synapses, and thus resembled the predominant type of SP+ terminal. The second type contained round clear vesicles and made asymmetric synapses, the third type contained medium-size pleomorphic clear vesicles and made symmetric synapses, and the fourth type contained small pleomorphic clear vesicles and made symmetric synapses. The presence of contacts between SP+ terminals and dopaminergic dendrites in the substantia nigra was directly demonstrated in tissue double-labeled for SP (by the peroxidase-antiperoxidase procedure, or PAP, with diaminobenzidine) and TH (by either the silver-intensified immunogold procedure or the PAP procedure with benzidine dihydrochloride). SP+ terminals commonly contacted thin TH+ dendrites in the substantia nigra, but few SP+ terminals contacted large-diameter TH+ dendrites or perikarya. Synapses between SP+ terminals and TH+ neurons were always symmetric. TH+ dendrites also were contacted by terminals not labeled for SP, which were more abundant than were SP+ terminals. Non-TH+ neurons were also contacted by both SP+ terminals and non-SP+ terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Striatonigral projection neurons: a retrograde labeling study of the percentages that contain substance P or enkephalin in pigeons.

Two largely separate populations of neuropeptide-containing striatonigral projection neurons have been distinguished in pigeons, one population whose neurons contain substance P (SP) and dynorphin (DYN) and a second population whose neurons contain enkephalin (ENK) (Reiner, '86a; Anderson and Reiner, '90a). In the present study, we investigated the abundance of these two types of neurons relative to all striatonigral projection neurons by combining retrograde labeling by the fluorescent dye fluorogold with immunofluorescence labeling for SP and ENK. Pigeons received large intranigral injections of fluorogold to retrogradely label the striatonigral projection neurons, and several days later they were treated with colchicine (32 hours before transcardial perfusion). Adjacent series of sections through the basal ganglia were labeled for SP and ENK using immunofluorescence techniques. The tissue was examined using fluorescence microscopy and the percentages of retrogradely labeled neurons containing either SP or ENK were quantified. We found that 85-95% of the fluorogold-labeled striatonigral neurons were SP+, whereas only 1-4% were ENK+. Thus the majority of striatonigral projection neurons in pigeons appear to contain SP, whereas a small percentage contain ENK. Only a small percentage of striatonigral neurons did not contain either. Since striatal projection neurons also contain GABA (Reiner, '86b), the present results suggest that a high percentage of striatonigral projection neurons coexpress SP, DYN and GABA, whereas a small fraction coexpress ENK and GABA. The available data are consistent with the conclusion that this is true in reptilian and mammalian species as well.

Animals↗
PubMed1991

Retroviral vector-mediated in vivo expression of low-density-lipoprotein receptors in the Watanabe heritable hyperlipidemic rabbit.

We have achieved in vivo expression of recombinant low-density-lipoprotein (LDL) receptors in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for the human disease familial hypercholesterolemia. A retroviral vector was constructed containing the human LDL receptor cDNA and was used to stably transduce primary skin fibroblasts from WHHL rabbits. The integrity and function of the introduced LDL receptor was established by immunoprecipitation, by a fluorescent LDL binding assay, and by the ability of the transduced cells to suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity in response to exogenous cholesterol. Autologous transduced fibroblasts were reimplanted into donor rabbits; in vivo LDL receptor expression and the survival of the transduced cells were analyzed by immunohistochemistry and by LDL binding assays performed on cells recovered from the implants. LDL receptor-bearing cells could be identified on tissue sections and recovered from implants for up to four weeks. Total and LDL cholesterol levels decreased significantly after implantation of the transduced cells; however, control experiments indicated that the decreases were not mediated through the recombinant LDL receptor. While in vivo stable expression of recombinant LDL receptors in Watanabe rabbits is possible, consequent changes in lipid levels must be interpreted with caution. This system of site-specific in vivo expression of recombinant LDL receptors permits further evaluation of the role of LDL receptor-gene replacement in the therapy of hypercholesterolemia.

Animals↗