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Biomedical subjects

C A Palmer

Publications and source records attributed to C A Palmer.

At least 19 recordsLinked to original sources

Functional regulation of xanthine oxidoreductase expression and localization in the mouse mammary gland: evidence of a role in lipid secretion.

Xanthine oxidoreductase (XOR), a key enzyme of purine metabolism, has been implicated in the secretion of the milk fat droplet in lactating mammary epithelial cells, possibly through structural interactions with other milk fat globule proteins including butyrophilin (Btn) and adipophilin (ADPH). To help determine the mechanism by which XOR is regulated, we examined the expression and localization of XOR in the non-secretory states of late pregnancy and induced involution compared with the state of active secretion. XOR mRNA levels started to increase at mid-pregnancy, turned sharply upwards at the onset of lactation and decreased rapidly with forced involution, indicating transcriptional control of the enzyme level by differentiation and secretory function. During pregnancy and involution the enzyme was diffusely distributed in the cytoplasm, but moved rapidly to the apical membrane of the cells when secretion was activated, where it colocalized with both Btn and ADPH, similar to the situation in the milk fat globule itself. Size-exclusion chromatography of solubilized milk fat globule membrane proteins showed that XOR formed a sulphydryl-bond-dependent complex with Btn and ADPH in the milk fat globule membrane. XOR returned to a diffuse cytoplasmic localization shortly after induced involution, while Btn remained localized to the apical membrane, suggesting that localization of XOR is not dependent on the presence of Btn in the apical membrane. Our findings indicate that the expression and membrane association of XOR in the mammary gland are tightly regulated by secretory activity, and suggest that the apical membrane association of XOR regulates the coupling of lipid droplets to the apical plasma membrane during milk lipid secretion.

Animals↗

Exuberant transverse ligament degeneration causing high cervical myelopathy.

Two patients with cervical myelopathy and C1-C2 retro-odontoid masses were examined. Preoperative magnetic resonance imaging studies suggested soft tissue pannus, as might be seen in rheumatoid arthritis; however, the results of serologic testing for rheumatoid factor were negative in both patients. Intraoperative findings and pathologic examination revealed degenerative fibrocartilage without inflammation or neoplasia. Similar lesions reported in the literature have been described as retro-odontoid disk hernia, damaged transverse ligaments, transverse ligament degeneration, synovial cysts, ganglion cysts, and degenerative articular cysts. These lesions may share a common pathophysiologic origin and represent a single disease process, namely exuberant degeneration of the transverse ligament.

Aged↗

Histological appearance of a chronically stimulated vagus nerve in a pediatric patient.

Histological analysis of chronically stimulated human vagus nerves is lacking in the literature. In this study, we describe the first microscopic findings in a chronically stimulated left vagus nerve from a pediatric patient. Our results show many histological changes in and around the stimulated nerve with severe demyelination. Further long-term clinical and postmortem examinations of chronically stimulated vagus nerves in both children and adults are needed to ascertain whether prolonged exposure to electrical current can cause clinical dysfunction of this nerve.

Brain↗

Neuropathology of occipital horn syndrome.

Occipital horn syndrome, formerly known as Ehlers-Danlos syndrome type IX or X-linked cutis laxa, is an allelic variant of Menkes' syndrome. Although the clinical symptomatology and systemic pathology findings have been well described in occipital horn syndrome, the neuropathology has not previously been reported. A kindred affected by the X-linked occipital horn syndrome is followed at the University of Alabama at Birmingham. A severely mentally retarded dysmorphic man, who died at the age of 26 years, never gained the ability to walk or talk. Among other findings at autopsy, the patient had the skeletal anomalies previously described with occipital horn syndrome. Neuropathologic findings included neovascularization and extreme reduplication of the cerebral arteries, in conjunction with cystic medial degeneration; bilateral cerebellar hypoplasia; focal cortical dysplasia, and cerebellar heterotopias. These findings are similar to those seen in the brains of patients with Menkes' syndrome, which is not surprising, given the known phenotypic overlap and the proven allelism of occipital horn syndrome with classic Menkes' syndrome.

Adolescent↗

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial.

G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both gamma(1)34.5 loci and a lacZ insertion disabling the UL39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score > or = 70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter. Serial magnetic resonance images were obtained for volumetric analysis. The trial commenced at a dose of 10(6) plaque forming units (p.f.u.) inoculated at a single enhancing site and was completed when the 21st patient was inoculated with 3x10(9) p.f.u. at five sites. While adverse events were noted in some patients, no toxicity or serious adverse events could unequivocally be ascribed to G207. No patient developed HSV encephalitis. We found radiographic and neuropathologic evidence suggestive of anti-tumor activity and long-term presence of viral DNA in some cases.

Adult↗

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Adult↗

Dietary determinants of dental caries and dietary recommendations for preschool children.

OBJECTIVES: The purpose of this review, commissioned by the Administration for Children and Families, the Health Resources and Services Administration, the Health Care Financing Administration, and the Department of Agriculture's Food and Nutrition Service, was to update the evidence of the dietary factors that affect dental caries, and subsequently formulate dietary recommendations for preschool children based on principles of cariology. METHODS: Literature on the dental caries process, dietary factors affecting dental caries initiation and progression, and nutrition education and counseling were reviewed and synthesized. Dietary guidelines for children at various ages were then constructed based on the review. RESULTS: Dental caries in preschool children is due to a combination of factors, including colonization of teeth with cariogenic bacteria, type of foods and frequency of exposure of these foods to the cariogenic bacteria, and susceptible teeth. Caries risk is greatest if sugars are consumed at high frequency and are in a form that is retained in the mouth for long periods. Sucrose is the most cariogenic sugar because it can form glucan that enables firm bacterial adhesion to teeth and limits diffusion of acid and buffers in the plaque. There is emerging interest in the effects of tooth development and its role in the future dental caries risk of the child. CONCLUSIONS: Nutrition education and counseling for the purposes of reducing caries in children is aimed at teaching parents the importance of reducing high frequency exposures to obvious and hidden sugars. Guidelines include: avoiding frequent consumption of juice or other sugar-containing drinks in the bottle or sippy cup, discouraging the behavior of a child sleeping with a bottle, promoting noncariogenic foods for snacks, fostering eating patterns consistent with the Food Guide Pyramid, limiting cariogenic foods to mealtimes, rapidly clearing cariogenic foods from the child's oral cavity either by toothbrushing or by consumption of protective foods, and restricting sugar-containing snacks that are slowly eaten (e.g., candy, cough drops, lollipops, suckers). Along with nutritional factors, a comprehensive approach to preventing dental caries in preschool children must include improved general dietary habits, good oral hygiene, appropriate use of fluorides, and access to preventive and restorative dental care.

Bacteria↗

The guilty but mentally ill verdict: a review and conceptual analysis of intent and impact.

The purpose of this article is to review the law and literature involving the guilty but mentally ill (GBMI) verdict to provide a clear conceptual examination of the actual intent and impact of the verdict. Such an examination may help to clarify continuing debates and confusion about the nature of GBMI and its success in addressing perceived problems with insanity acquittals. This review suggests that the actual intentions of the GBMI verdict are associated with minimal and largely unsuccessful results. In addition, the typical absence of treatment for defendants found GBMI appears unsurprising given that the provision of treatment for mentally ill offenders is not a legal intention of the GBMI verdict. Finally, the introduction of the GBMI verdict has had unintended negative consequences that include increased confusion among jurors and the legal profession and possible increased occurrence of inappropriate verdicts. In conclusion, significant problems can be noted with regard to both the intent and impact of the GBMI verdict.

Crime↗

Rapid appraisal of needs in reproductive health care in southern Sudan: qualitative study.

OBJECTIVES: To identify the need for reproductive health care among a community affected by conflict, and to ascertain the priority given by the community to reproductive health issues. DESIGN: Rapid appraisal. This comprised interviews with key informants, in-depth interviews, and group discussions. Secondary data were collated. Freelisting, ranking, and scenarios were used to obtain information. SETTING: Communities affected by conflict in southern Sudan. PARTICIPANTS: Interviews and group discussions were chosen purposively. Twenty interviews with key informants were undertaken, in-depth interviews were held with 14 women, and 23 group discussions were held. MAIN OUTCOME MEASURES: Need for reproductive health care. Perceived priority afforded to reproductive health issues in comparison with other health problems. RESULTS: Reproductive health in general and sexually transmitted diseases in particular were important issues for these communities. Problems in reproductive health were ranked differently depending on the age and sex of the respondents. Perceptions about reproductive health issues in communities varied between service providers, and community leaders. Settled and displaced communities had different priorities and differing experiences of reproductive health problems and their treatment. CONCLUSION: Rapid appraisal could be used as the first step to involving communities in assessing needs and planning service provision.

Age Distribution↗

Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: a tool for rapid screening of new compounds for metabolic stability.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic parameters. One useful parameter that can be measured in vitro using liver microsomal preparations is metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal samples for a series of compounds. This system is based on the Sciex API 150 (single quadrupole) liquid chromatography/mass spectrometry system and utilizes 96-well plate autosampler technology as well as a custom-designed AppleScript which executes the on-line data processing and report generation. It has the capability of analyzing at least 75 compounds per week or 300 compounds per month in an automated fashion.

Autoanalysis↗

The emerging international policy agenda for reproductive health services in conflict settings.

Over the past 20 years, shifts in the nature of conflict and the sheer numbers of civilians affected have given rise to increasing concern about providing appropriate health services in unstable settings. Concurrently, international health policy attention has focused on sexual and reproductive health issues and finding effective methods of addressing them. This article reviews the background to the promotion and development of reproductive health services for conflict-affected populations. It employs qualitative methods to analyse the development of policy at international level. First we examine the extent to which reproductive health is on the policy agendas of organisations active in humanitarian contexts. We then discuss why and how this has come about, and whether the issue has sufficient support to ensure effective implementation. Our findings demonstrate that reproductive health is clearly on the agenda for agencies working in these settings, as measured by a range of established criteria including the amount of new resources being attracted to this area and the number of meetings and publications devoted to this issue. There are, however, barriers to the full and effective implementation of reproductive health services. These barriers include the hesitation of some field-workers to prioritise reproductive health and the number and diversity of the organisations involved in implementation. The reasons for these barriers are discussed in order to highlight areas for action before effective reproductive health service provision to these populations can be ensured.

Conflict of Interest↗

Spinal cord hamartoma: case report.

OBJECTIVE AND IMPORTANCE: Spinal cord hamartomas are infrequently mentioned in the literature. The authors present a unique report detailing the clinical presentation of a spinal cord hamartoma, with supporting radiographic and pathological data. CLINICAL PRESENTATION: A 26-year-old man presented with progressive right upper extremity weakness. Imaging studies revealed an exophytic cervical spinal cord mass. INTERVENTION: Open biopsy was undertaken and revealed tethering of the lesion to the dura. A pathological examination revealed a spinal cord hamartoma. CONCLUSION: The patient's symptoms improved postoperatively, suggesting that tethering of the spinal cord was responsible for the symptoms. Although unusual, hamartoma should be included in the differential diagnosis of an exophytic spinal cord lesion.

Adult↗

The safety of OP-1 for lumbar fusion with decompression-- a canine study.

OBJECTIVE: Bone morphogenetic proteins can serve as adjuncts to autologous bone to achieve bony fusion, and recombinant BMPs such as osteogenic protein-1 (OP-1) have the potential to replace autologous bone altogether as fusion substrate. However, relatively little is known about the safety of OP-1 for spinal fusion procedures. This study examined the effects of OP-1 intentionally placed in the subarachnoid space following thecal sac decompression, and used as graft substrate in a canine dorsolateral lumbar spine fusion model. METHODS: Lumbar decompression with dorsolateral fusion was performed on 30 canines. The dura was opened to simulate an intraoperative rent and OP-1 was placed in the subarachnoid space and in the fusion bed. Animals were sacrificed after 16 weeks and the spines were examined manually, radiographically and pathologically. RESULTS: All animals treated with OP-1 developed new bone in the subarachnoid space. This bone compressed the spinal cord, but no clinical or pathological features of neurotoxicity were noted. Mild spinal stenosis was noted at the site of dural decompression in the OP-1 treated animals. Over 80% of animals treated with OP-1 developed fusion as assessed by palpation (52% by CT criteria), while only 25% of control animals fused. CONCLUSIONS: Recombinant human OP-1 is effective at promoting fusion in a canine dorsolateral lumbar spine fusion model. However, bone growth can occur over exposed, decompressed dura, and it can form in the subdural and subarachnoid spaces. The use of OP-1 as an adjunct to spinal fusion appears to have merit, but its use must be carefully controlled to avoid unwanted bone formation and subsequent neural compression.

Animals↗

Rasmussen's encephalitis with concomitant cortical dysplasia: the role of GluR3.

The role of the glutamate receptor GluR3 in Rasmussen's encephalitis is actively under investigation. Autoimmune processes with this receptor as the target are currently theorized. We provide an additional case of pathologically proved Rasmussen's encephalitis (with concomitant cortical dysplasia) in the presence of antibodies against the GluR3 receptor.

Autoimmune Diseases↗

Method of preparing emergency medicine residents for giving legal depositions.

This study was performed to determine if a simulated legal deposition increases emergency medicine (EM) residents' knowledge, self-confidence, and understanding of a legal deposition. This prospective study included a convenience sample of EM 1-3 residents. A knowledge and a self-assessment pretest were given, followed by a didactic session moderated by local attorneys, followed by knowledge and a self-assessment posttest. The total time involved was 2 hours. The mean score on the knowledge pretest was 4.5 and 5.25 on the posttest. Using a paired t-test, the authors found this difference to be statistically significant. (P < 0.01) Using Hotelling's T2 test, the authors compared presimulation and postsimulation self-assessment questions. The results revealed that there was a difference between these scores (P < 0.001). Participants in the deposition significantly improved their self-assessment ranking and knowledge inventory test scores by participating in a simulated legal deposition.

Adult↗

Women, health and humanitarian aid in conflict.

The burden of political conflict on civilian populations has increased significantly over the last few decades. Increasingly, the provision of resources and services to these populations is coming under scrutiny; we highlight here the limited attention to gender in their provision. Women and men have different exposures to situations that affect health and access to health-care and have differential power to influence decisions regarding the provision of health services. We argue that the role of women in planning is central to the provision of effective, efficient and sensitive health-care to conflict-affected populations.

Africa↗

Two cases of cerebral aneurysms in HIV+ children.

Two cases of fusiform cerebral aneurysms in human immunodeficiency virus (HIV) positive children are presented. To our knowledge, only 9 patients with this association have been reported. One of our patients represents the first report of a patient with an aneurysm associated with varicella-zoster vasculitis. One patient presented with a subarachnoid hemorrhage, Hunt-Hess grade IV, and posed difficult surgical management. The other patient suffered a cerebral infarct with a resulting hemiparesis. The first patient had a ventriculostomy placed, initially improved, and subsequently died from rebleeding. The second patient improved with medical management. AIDS arteriopathy, and specifically fusiform aneurysms, are being increasingly reported. The various presentations of this surgically challenging entity in light of other AIDS-related syndromes pose difficult management decisions. On occasion, the intracranial aneurysm may be the initial form of presentation as was present in our first patient.

Cerebral Arteries↗

Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.

OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. RESULTS: The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. CONCLUSION: These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.

Adult↗