Search PubMed⌕ Search

Biomedical subjects

J A Golden

Publications and source records attributed to J A Golden.

At least 55 records · Page 3Linked to original sources
PubMed1998

Groups of histopathologic abnormalities in brains of very low birthweight infants.

The neuropathologic changes in brains of very premature infants are well recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury. The goal of this study is to identify which, if any, combinations of histologic features occur together. We identified the presence or absence of 19 histologic features in the brains of 67 infants from a multicenter study of 1,665 prematurely born infants whose birthweight was 500-1,500 grams. We used clustering algorithms and factor analysis to group pathologic features that occurred together. Our results indicate that certain histopathologic features do cluster. For example, telencephalic white matter astrocytosis occurs in 2 groups: 1) associated with amphophilic globules, and, 2) in an uncorrelated group, associated with focal macrophage deposits and coagulative necroses. Parenchymal hemorrhage was not found to be associated with any telencephalic leukoencephalopathy, regardless of whether characterized by rarefaction, astrocytosis, focal coagulative necroses, or foci of macrophages in the white matter. Intraventricular hemorrhage and germinal matrix hemorrhage were not seen together more often than by chance expectation. Intraventricular hemorrhage was only marginally associated with parenchymal hemorrhage. Our data indicate that specific histopathologic features tend to preferentially cluster with each other in groups. This clustering may represent the manifestation of a common mechanism for each. These data should be valuable indicators for future research attempting to establish pathogenesis.

Algorithms↗
PubMed1998

Expandable metallic stents in benign tracheobronchial obstruction.

Expandable metallic stents offer advantages over previously available techniques for treating benign tracheobronchial stenosis or obstruction. Endoluminal stent placement offers a rapid and effective means of opening up narrowed airways, and results in excellent relief of symptoms and improvement in pulmonary function. Because they are delivered in a nonexpanded state using flexible over-wire systems, they can be placed using a flexible bronchoscope and can be located in second-order bronchial branches. Metallic stents have been used to treat benign airway obstruction caused by anastomotic narrowing after lung transplantation, infection, congenital lesions, tracheobronchial malacia, inflammatory conditions including relapsing polychondritis, Wegener granulomatosis, and acquired immunodeficiency syndrome, and external compression from benign mediastinal masses or fibrosis. The stents become epithelialized, which prevents migration and permits ciliary activity to continue. Significant complications can occur, including airway inflammation, stent migration, airway erosion, and stent fracture and collapse, but more serious complications are uncommon. Computed tomography is essential in imaging patients being considered for stent placement, as it allows 1) accurate representation of airway anatomy in three dimensions. 2) measurement of airway diameter, 3) evaluation of airway anatomy distal to a narrowed segment and invisible to bronchoscopy, 4) demonstration of dynamic changes in airway morphologic features during forced exhalation in patients with airway malacia, and 5) demonstration of focal or diffuse air trapping in lung peripheral to the abnormal airway. In patients who have had stent placement, computed tomography is valuable in assessing airway morphologic features and dynamics distal to the stent, and can be valuable in assessing stent dysfunction.

Airway Obstruction↗
PubMed1998

Surgical removal of a choroid plexus adenoma using the argon beam coagulator: technical case report.

OBJECTIVE AND IMPORTANCE: Choroid plexus tumors may be extremely vascular, limiting surgical resection. A case of a choroid plexus adenoma is presented in which the argon beam coagulator (System 6500; ConMed Corp., Utica, NY) was used as a surgical adjunct. CLINICAL PRESENTATION: A 12-year-old male patient with a giant tumor of the lateral ventricle presented with visual loss and was found to have a large intraventricular tumor. At surgery, the tumor was extremely vascular, and the pathological finding was consistent with a choroid plexus adenoma. TECHNIQUE: Because of its vascularity, the tumor was resected in stages with the aid of the argon beam coagulator. CONCLUSION: We conclude that this device may have application in selected neurosurgical operations.

Adenoma↗
PubMed1998

Möbius syndrome with oculomotor nerve paralysis without abducens paralysis.

Möbius syndrome is typified by bilateral facial nerve palsies, usually with abducens palsies. We examined an infant with Möbius syndrome who had bifacial weakness and third nerve palsies, but intact abduction of both eyes. Lower cranial nerve involvement, leading to respiratory, swallowing, and cardiac difficulties, was also present. Pathologic examination of the brainstem showed absent or hypoplastic third, seventh, tenth, and twelfth nerve nuclei. The fourth, fifth, sixth, and eighth nerve nuclei were intact. In Möbius syndrome with ocular motor palsies, rarely the sixth nerve may be spared.

Abducens Nerve↗
PubMed1997

Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing.

Several X-linked disorders affect females disproportionately or exclusively. These including focal dermal hypoplasia, oral-facial-digital syndrome type I (ref. 3) and epilepsy with bilateral periventricular heterotopias. X-linked dominant inheritance with male lethality is probably responsible for sex-limited expression of these disorders, as affected women have frequent spontaneous abortions and the sex ratio of their live offspring is often skewed. The same inheritance pattern has been proposed for Rett syndrome, Aicardi syndrome and microphthalmia with linear skin defects, but in these sporadic conditions, evidence of male lethality is lacking. We investigated an unusual family with epilepsy and mental retardation limited to females (EFMR, #121250 in ref. 9); this disorder is transmitted both by females and by completely unaffected carrier males. Assignment of the EFMR disease locus (EFMR) to the X chromosome indicates that selective involvement of females in X-linked disease may in some instances result from male sparing rather than male lethality.

Cerebral Cortex↗
PubMed1997

Frequency of neuropathological abnormalities in very low birth weight infants.

The occurrences of histologic changes in the central nervous system of very low birth weight infants (500 to 1500 grams) according to gestational age and postnatal age are incompletely reported. In order to better understand the abnormalities present in this patient population, the brains of 67 very low birth weight infants who died after having had at least one cranial ultrasound scan were studied. More than half the infants were born at gestational ages of 24 to 26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who had to agree on the presence and/or absence of each histologic characteristic. Among infants who died within 24 h of birth, fully one quarter had parenchymal hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20% had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury to the nervous system was common. Compared with infants who died before the sixth day, those who survived at least 6 days were twice as likely to have moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than those who died before the 7th postnatal day. Parenchymal hemorrhage and moderate/severe ventriculomegaly decreased in frequency with increasing gestational age. On the other hand, the older the gestational age, the higher the likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage foci, and zones of coagulative necrosis upon neuropathologic examination. Our data indicate that several central nervous system abnormalities appear to increase with both older gestational age and older postnatal age for infants born weighing less than 1500 grams. We were unable, however, to determine the relative contribution of gestational age and postnatal age to the specific neuropathologic findings in this study.

Aging↗
PubMed1997

Cell migration in the developing chick diencephalon.

We previously reported that retrovirally marked clones in the mature chick diencephalon were widely dispersed in the mediolateral, dorsoventral and rostrocaudal planes. The current study was undertaken to define the migration routes that led to the dispersion. Embryos were infected between stages 10 and 14 with a retroviral stock encoding alkaline phosphatase and a library of molecular tags. Embryos were harvested 2.5-5.5 days later and the brains were fixed and serially sectioned. Sibling relationships were determined following PCR amplification and sequencing of the molecular tag. On embryonic day 4, all clones were organized in radial columns spanning the neuroepithelium, which was composed primarily of a ventricular zone at this age. No tangential migration was seen in the ventricular zone. On embryonic day 5, most clones remained radial with many cells located in the ventricular zone; however, a few clones had cells migrating perpendicular to the radial column, in either a rostrocaudal or dorsoventral direction. The tangential migration began just beyond the basal limit of the ventricular zone. On embryonic days 6 and 7, many clones had cells migrating perpendicular to the radial column, which spanned from the ventricular to the pial surface. The migrating cells appeared to be aligned along axes that were perpendicular to the radial column. Using a combination of DiI tracing, immunohistochemistry and electron microscopy, we have determined that axonal tracts are present and are aligned with the migrating cells, suggesting that they support the non-radial cell migration. These data indicate that migration along pathways independent of radial glia occur outside of the ventricular zone in more than 50% of the clones in the chick diencephalon.

Animals↗
PubMed1997

Pulmonary alveolar proteinosis: high-resolution CT, chest radiographic, and functional correlations.

STUDY OBJECTIVE: To determine whether a correlation exists between pulmonary function and both frontal chest radiographs and high-resolution chest CT findings in patients with pulmonary alveolar proteinosis (PAP). DESIGN: Retrospective review of radiographic and clinical data. SETTING: Tertiary referral hospital. PATIENTS: Seven patients with PAP were studied on 25 occasions using high-resolution chest CT (n=21), frontal chest radiographs (n=19), and pulmonary function tests (PFTs) (n=25). MEASUREMENTS AND RESULTS: Visual estimates of the extent, degree, and overall severity of parenchymal abnormalities were determined for plain radiographs and high-resolution chest CT, and were correlated with PFTs. With high-resolution CT, the extent and severity of ground-glass opacity correlated significantly with the presence of a restrictive ventilatory defect, reduced diffusing capacity, and hypoxemia. Chest radiographic findings also correlated significantly with restrictive ventilatory defect, diffusing capacity, and hypoxemia. CONCLUSION: In patients with PAP, although high-resolution CT correlates more closely with pulmonary function, plain radiographs should be sufficient for follow-up.

Adult↗
PubMed1996

Semaphorin III is needed for normal patterning and growth of nerves, bones and heart.

The expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development. Some seem to guide neuronal growth cones, but otherwise their functions are unknown. Semaphorin III is a membrane-associated secreted protein with a developmentally dynamic pattern of expression, including particular domains of the nervous system, the borders of developing bones, and the heart. In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord. Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident. We have generated mice mutant in the semaIII gene by homologous recombination. Here we show that in the mutants, some sensory axons project into inappropriate regions of the spinal cord where semaIII is normally expressed. The cerebral cortex of homozygous mutant mice shows a paucity of neuropil and abnormally oriented neuronal processes, especially of the large pyramidal neurons. Certain embryonic bones and cartilaginous structures develop abnormally, with vertebral fusions and partial rib duplications. The few mice that survive more than a few days postnatally manifest pronounced and selective hypertrophy of the right ventricle of the heart and dilation of the right atrium. Thus, semaphorin III might serve as a signal that restrains growth in several developing organs.

Animals↗
PubMed1996

Progenitor cell proliferation outside the ventricular and subventricular zones during human brain development.

The ventricular zone (VZ) and subventricular zone (SVZ) of the fetal brain are generally believed to give rise to all the neurons and glia that will populate the cerebral hemispheres. In rodents a mitotically active cell (progenitor cell) has been identified outside the VZ and SVZ, in the intermediate zone (IZ) of the cerebral hemisphere. The cell types that arise from these progenitor cells remain uncertain. We have set out to determine if a similar population of mitotically active cells is present in the IZ during human brain development, and to try and define the cell type that arise from this progenitor cell. Using a monoclonal antibody that recognizes proliferating cell nuclear antigen (PCNA), a replication-specific protein, the cerebral hemispheres from 9 human fetal and infant brains between ages of 15 and 38 weeks gestation were studied. PCNA-immunopositive cells were found in the internal capsule and cerebral white matter with approximately equal frequency and rarely in the cerebral cortex between 15 and 20 weeks gestation. In the internal capsule, the number of positive cells decreased by the end of the second trimester; however, a relatively constant number of PCNA-positive cells remained in the cerebral white matter. By the last trimester relatively little staining was found in any of the regions studied. Anti-GFAP immunostaining indicated that at least some of these progenitors were in the glial lineage. These data provide direct evidence that, in addition to ventricular zone proliferation, a population of progenitor cells continue to proliferate within nascent white matter tracts during development.

Brain↗
PubMed1996

Clones in the chick diencephalon contain multiple cell types and siblings are widely dispersed.

The thalamus, hypothalamus and epithalamus of the vertebrate central nervous system are derived from the embryonic diencephalon. These regions of the nervous system function as major relays between the telencephalon and more caudal regions of the brain. Early in development, the diencephalon morphologically comprises distinct units known as neuromeres or prosomeres. As development proceeds, multiple nuclei, the functional and anatomical units of the diencephalon, derive from the neuromeres. It was of interest to determine whether progenitors in the diencephalon give rise to daughters that cross nuclear or neuromeric boundaries. To this end, a highly complex retroviral library was used to infect diencephalic progenitors. Retrovirally marked clones were found to contain neurons, glia and occasionally radial glia. The majority of clones dispersed in all directions, resulting in sibling cells populating multiple nuclei within the diencephalon. In addition, several distinctive patterns of dispersion were observed. These included clones with siblings distributed bilaterally across the third ventricle, clones that originated in the lateral ventricle, clones that crossed neuromeric boundaries, and clones that crossed major boundaries of the developing nervous system, such as the diencephalon and mesencephalon. These findings demonstrate that progenitor cells in the diencephalon are multipotent and that their daughters can become widely dispersed.

Alkaline Phosphatase↗
PubMed1995

Construction and characterization of a highly complex retroviral library for lineage analysis.

Replication-incompetent retroviral vectors encoding histochemical reporter genes have been used for studying lineal relationships in a variety of species. A crucial element in the interpretation of data generated by this method is the identification of sibling relationships, or clonal boundaries. The use of a library of viruses in which each member is unique can greatly facilitate this aspect of the analysis. A previously reported murine retroviral library containing about 80 members demonstrated the utility of the library approach. However, the relatively low number of tags in the murine library necessitated using low infection rates in order to give confidence in clonal assignments. To obviate the need for low infection rates, a far more complex library was created and characterized. The CHAPOL library was constructed such that each member encodes a histochemical reporter gene and has a DNA tag derived from a degenerate oligonucleotide pool synthesized to have a complexity of > 1 x 10(7). The library was tested after infection of cells in vitro or in vivo. The DNA tag from each histochemically labeled cell or clone of cells was recovered by PCR and sequenced for unambiguous identification. Three hundred and twenty tags have been identified after infection, and so far no tag has been seen to result from more than one independent infection. Thus, an equal distribution of inserts is suggested, and Monte Carlo analysis predicts a complexity of > 10(4) members.

Animals↗
PubMed1995

The neuropathology of Williams syndrome. Report of a 35-year-old man with presenile beta/A4 amyloid plaques and neurofibrillary tangles.

OBJECTIVE: To study neuropathologically Williams syndrome in a 35-year-old patient. METHODS: Sections from multiple regions of the brain were examined with luxol fast blue and hematoxylineosin staining, and selected sections were stained with the silver impregnation technique (Bielschowsky technique) and Congo red. In addition, immunohistochemistry with monoclonal antibodies against glial fibrillary acidic protein, beta/A4 amyloid, paired helical filaments, and phosphorylated tau protein was performed on cortical, hippocampal, amygdaloid, and basal ganglian sections. RESULTS: No specific macroscopic or microscopic abnormalities were recognized that are specific for Williams syndrome. The histopathologic examination did, however, demonstrate the presence of Alzheimer-type changes, including beta/A4 amyloid-containing senile plaques and scattered neurofibrillary tangles in neocortex and medial temporal lobe structures (entorhinal cortex, CA1 area of the hippocampus, and amygdala). Plaques were most numerous in the amygdala (7/mm2) and in the entorhinal cortex (4/mm2). Neurofibrillary tangles were less numerous (< 1/mm2), except in the hippocampus, where approximately 2/mm2 were found. CONCLUSIONS: To our knowledge, ours represents the first neuropathologic description of a patient with Williams syndrome. Although Williams syndrome is usually sporadic, familial cases have been reported along with candidate chromosomal loci. If our findings are confirmed in additional patients with Williams syndrome, they may provide clues to other factors that are important in the pathogenesis of senile plaques (with beta/A4 amyloid deposition) and neurofibrillary tangles.

Adult↗
PubMed1995

Intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine used for prophylaxis of pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus.

A study was conducted to determine the intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine prophylaxis (APP) in patients infected with human immunodeficiency virus (HIV). 151 patients received high-dose (300 mg twice a month or 600 mg once a month) APP as part of a previously published clinical trial, and 29 additional patients received standard-dose (300 mg once a month) APP. Serial blood samples were obtained from the first cohort: 577 samples were obtained from 76 patients in the group given 600 mg once a month, and 554 blood samples were obtained from 75 patients in the group given 300 mg twice a month. In 9 of the 151 patients, bronchoscopy and tri-lobar (right upper, middle, and lower lobe) bronchoalveolar lavage (BAL) were performed 6 and 12 months after initiation of APP. Unilobar (right middle lobe) BAL was performed in the 29 patients infected with HIV who underwent bronchoscopy for diagnostic purposes. Pentamidine was measured using a chromatographic (HPLC) assay. The concentrations (mean +/- SD) of pentamidine in plasma in the groups given 300 mg twice a month and 600 mg once a month were 5.3 +/- 6.1 ng/mL and 8.8 +/- 9.6 ng/mL, respectively, and accumulation did not occur. The BAL supernatant and alveolar cell pentamidine concentrations were not significantly different in the 3 lobes and ranged from 16.5 +/- 7.7 ng/mL to 29.2 +/- 19.5 ng/mL and 1255 +/- 1142 ng/mg protein to 1572 +/- 1161 ng/mg protein in the group given 300 mg twice a month; and from 5.5 +/- 2.9 ng/mL to 9.4 +/- 7.7 ng/mL and 339 +/- 201 ng/mg protein to 571+/- 681 ng/mg protein in the group given 600 mg once a month. The intropulmonary concentrations of pentamidine at 6 and 12 months were not significantly different. In 18 of the 29 patients who received 1 to 7 prior monthly doses of standard APP, drug concentrations in BAL increased linearly (y = 2.05x) with the number of doses administered before bronchoscopy. These data indicate that intrapulmonary drug concentrations continue to increase for approximately 6 months after the initiation of APP, at which time steady state is achieved, and that administration of high dose APP is probably safe.

AIDS-Related Opportunistic Infections↗
PubMed1995

Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin.

The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four of the subjects, two in the clarithromycin group and two in the erythromycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8, 12, 24, and 48 h after administration of the last dose of clarithromycin and at 4, 8, and 12 h after administration of the last dose of erythromycin. Clarithromycin was measured by high-performance liquid chromatography, and erythromycin was measured by a microbiological assay. No systemic sedation was used. There were no major adverse events. The concentrations of antibiotics in epithelial lining fluid (ELF) were calculated by the urea dilution method. The volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7 ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered, the volume of ELF, or the number of erythrocytes present in the lavage fluid (P > 0.05 for all comparisons). The total number of alveolar cells, however, was almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05). Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 micrograms/ml at 8 h to 11.9 +/- 3.6 micrograms/ml at 24 h) and alveolar cells (range, 505.8 +/- 293.1 micrograms/ml at 4 h to 17.0 +/- 34.0 micrograms/ml at 48 h). 14-(R)-Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of erythromycin in ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug (range, 0 to 0.8 +/- microgram/ml in ELF and 0 to 0.8 +/- 1.3 microgram/ml in alveolar cells). The clinical significance of any antibiotic concentrations in these compartments in unclear. The data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caused by intracellular organisms.

Adult↗
PubMed1995

Hydrostatic pulmonary edema: high-resolution CT findings.

Hydrostatic pulmonary edema can be defined as an abnormal increase in extravascular water secondary to elevated pressure in the pulmonary circulation, as in congestive heart failure or intravascular volume overload. The diagnosis of hydrostatic pulmonary edema is usually based on clinical information, conventional chest radiograph findings, and response to treatment and does not require high-resolution CT. However, recognizing the appearance of hydrostatic pulmonary edema on high-resolution CT can be important, as the edema can mimic other diseases or can occur as an unsuspected finding in patients having high-resolution CT for other indications, and a misdiagnosis may lead to unnecessary lung biopsy. Although the CT appearances of pulmonary edema have been described in several studies [1-3], to date, the high-resolution CT appearances of hydrostatic pulmonary edema have been described only in isolated cases [4-6] or in experimental studies of phantom or animal models [7, 8]. This essay illustrates the spectrum of high-resolution CT findings seen in adult patients with hydrostatic pulmonary edema secondary to cardiac disease.

Aged↗
PubMed1995

Multiple sites of anterior neural tube closure in humans: evidence from anterior neural tube defects (anencephaly).

OBJECTIVE: Anterior neural tube closure in humans is thought to occur via a continuous process, culminating in the closure of the anterior neuropore. Recent studies have demonstrated that, in some species, the process is discontinuous, with four separate sites of closure initiation. In this study, we tested the hypothesis that humans, like mice and other experimental animals, have multiple sites of anterior neural tube closure. METHODS: Twenty human fetuses and neonates with open anterior neural tube defects were identified. The rostral and caudal boundaries of each defect was localized on a model cranium upon which was superimposed the four sites of anterior closure characterized in the mouse. RESULTS: Of the 20 cases, 7 (35%) defects involved the frontal region, 7 (35%) were limited to the parietal region, 4 (20%) to the occipital region, and 2 (10%) involved both the parietal and occipital regions. These defects clustered into discrete regions, corresponding to sites of closure in the mouse model. The location of the defects fell into two categories; those occurring at the junction of two closures, and those occurring within a single closure. CONCLUSION: The results of this study support the hypothesis that humans, like other species, have multiple sites of anterior neural tube closure. Furthermore, the data provide evidence for two mechanisms leading to anterior neural tube defects: one resulting from the failure of a closure to occur, and the second from the failure of two closures to meet. The findings provide insight into the variations observed in the location, recurrence risk, and etiologies of anterior neural tube defects in the human population.

Anencephaly↗