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Biomedical subjects

J Stone

Publications and source records attributed to J Stone.

At least 91 records · Page 5Linked to original sources
PubMed2000

Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics.

OBJECTIVES: To determine (a) the proportion of patients referred to general neurology outpatient clinics whose symptoms are medically unexplained; (b) why they were referred; (c) health status and emotional disorder in this group compared with patients whose symptoms are explained by "organic" neurological disease. METHODS: The prospective cohort study with case note follow up at 6 months was carried out in the regional neurology service in Lothian, Scotland with 300 newly referred outpatients. Neurologists rated the degree to which patients' symptoms were explained by organic disease (organicity), GPs' reasons for referral, health status (SF-36), anxiety, and depressive disorders (PRIME-MD), RESULTS: Of 300 new patients 11% (95% confidence interval (95% CI) 7%-14%) had symptoms that were rated as "not at all explained" by organic disease, 19% (15% to 23%) "somewhat explained", 27% (22% to 32%) "largely explained", and 43% (37% to 49%) "completely explained" by organic disease. Reason for referral was not associated with "organicity". Comparison of these groups showed that although physical function was similar, the median number of physical symptoms and pain were greater in patients with lower organicity ratings (p<0.0005, p<0. 0005). Depressive and anxiety disorders were more common in patients with symptoms of lower organicity (70% of patients in the not at all group had an anxiety or depressive disorder compared with 32% in the completely explained group (p<0.0005). CONCLUSION: One third of new referrals to general neurology clinics have symptoms that are poorly explained by identifiable organic disease. These patients were disabled and distressed. They deserve more attention.

Adolescent↗
PubMed2000

Fraud. What is the evidence?

The home health industry complains that Medicare fraud and abuse initiatives and legislation, namely, Operation Restore Trust (ORT), the Health Insurance Portability and Accountability Act (HIPAA) of 1996, and the Balanced Budget Act (BBA) of 1997 developed when home health care was vulnerable to reimbursement reductions from Medicaid and commercial insurers, particularly Health Maintenance Organizations. Additionally, it contends that the Health Care Financing Administration (HCFA) founded these initiatives on controversial government studies showing high rates of home health fraud and abuse and inappropriate assumptions that rising costs were indicative of fraudulent activities (Sarraille & William, 1998). We summarize reasons why the home health industry became a focus for enhanced Medicare fraud and abuse reduction efforts by HCFA and provide evidence supporting enforcement actions by HCFA's partners.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1999

Tissue oxygen levels control astrocyte movement and differentiation in developing retina.

Astrocytes play a key role in the development of retinal vessels by detecting hypoxia in developing retina and secreting the hypoxia-induced angiogenic factor VEGF to induce vessel formation. The astrocytes which play this role are themselves spreading over the retina, just ahead of the growing vessels. To understand the mechanisms which keep astrocytes in this strategic 'just ahead' position we have studied the effects of hyperoxia and hypoxia on astrocyte differentiation and movement in situ in neonatal rat retina and in primary culture. Hyperoxia in situ inhibited the stellation of astrocytes, so that they persisted in a relatively unbranched form, which accumulated at the edge of their spreading population; hyperoxia permitted but did not accelerate migration. Conversely, hypoxia induced unstellated astrocytes to stellate within 6 h. If the hypoxia was abnormally severe, it caused the astrocytes to hyperstellate and slowed their spread. Astrocytes in primary culture did not change morphology or motility when challenged by hypoxia. When treated with medium conditioned by retina however, astrocytes became mobile and, if the medium was conditioned by hypoxic retina, became stellate. These results suggest that the oxygen released by retinal vessels maintains the mobility of astrocytes, via a diffusible factor released by other retinal cells. Conversely, naturally generated hypoxia of developing retina plays a triple role, inducing astrocytes to stellate, to end their migration and to produce VEGF, thereby inducing vessel formation. The induction of stellation is mediated by a diffusible factor released by other retinal cells. Thus hypoxia of the retina generated by neural maturation induces key events in both the differentiation of astrocytes and the formation of blood vessels.

Aging↗
PubMed1999

Manipulations of ACHE gene expression suggest non-catalytic involvement of acetylcholinesterase in the functioning of mammalian photoreceptors but not in retinal degeneration.

To explore role(s) of acetylcholinesterase (AChE) in functioning and diseased photoreceptors, we studied normal (rd/+) and degenerating (rd/rd) murine retinas. All retinal neurons, expressed AChEmRNA throughout fetal development. AChE and c-Fos mRNAs peaked at post-natal days 10-12, when apoptosis of rd/rd photoreceptors begins. Moreover, c-Fos and AChEmRNA were co-overexpressed in rd/rd mice producing transgenic human (h), and host (m) AChE, but not in rd/+ mice. However, mAChE overexpression also occurred in transgenics expressing human serum albumin. Drastic variations in AChE catalytic activity were ineffective during development. Neither transgenic excess nor diisopropylfluorophosphonate (DFP) inhibition (80%) affected the rd phenotype; nor did DFP exposure induce photoreceptor degeneration or affect other key cholinergic proteins in rd/+ mice, unlike reports of adult mice and despite massive induction under DFP of c-Fos70 years). Therefore, the extreme retinal sensitivity to AChE modulation may reflect non-catalytic function(s) of AChE in adult photoreceptors. These findings exclude AChE as causing the rd phenotype, suggest that its primary function(s) in mammalian retinal development are non-catalytic ones and indicate special role(s) for the AChE protein in adult photoreceptors.

Acetylcholinesterase↗
PubMed1999

True hermaphroditism with partial duplication of chromosome 22 and without SRY.

We present the case of a patient with true hermaphroditism and partial duplication of chromosome 22. Cytogenetic evaluation showed no evidence of a Y chromosome in blood, skin, or gonadal tissue. Additional investigations using molecular probes showed no evidence of SRY. We conclude that there are genes on chromosome 22 that are involved in sex determination.

Base Sequence↗
PubMed1999

Contrast agent neurotoxicity presenting as subarachnoid hemorrhage.

A patient developed signs, symptoms, and radiologic findings compatible with acute subarachnoid hemorrhage after receiving a large dose of heparin and intravascular contrast medium for coronary angiography and stent placement. Subsequent CT indicated the subarachnoid enhancement was due to contrast. Neurotoxicity from contrast agents is well-known, however this is an unusual report of toxicity mimicking subarachnoid hemorrhage clinically and radiologically.

Aged↗
PubMed1999

Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial.

CONTEXT: Insomnia is a prevalent health complaint in older adults. Behavioral and pharmacological treatments have their benefits and limitations, but no placebo-controlled study has compared their separate and combined effects for late-life insomnia. OBJECTIVE: To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for late-life insomnia. DESIGN AND SETTING: Randomized, placebo-controlled clinical trial, at a single academic medical center. Outpatient treatment lasted 8 weeks with follow-ups conducted at 3, 12, and 24 months. SUBJECTS: Seventy-eight adults (50 women, 28 men; mean age, 65 years) with chronic and primary insomnia. INTERVENTIONS: Cognitive-behavior therapy (stimulus control, sleep restriction, sleep hygiene, and cognitive therapy) (n = 18), pharmacotherapy (temazepam) (n = 20), or both (n = 20) compared with placebo (n = 20). MAIN OUTCOME MEASURES: Time awake after sleep onset and sleep efficiency as measured by sleep diaries and polysomnography; clinical ratings from subjects, significant others, and clinicians. RESULTS: The 3 active treatments were more effective than placebo at posttreatment assessment; there was a trend for the combined approach to improve sleep more than either of its 2 single components (shorter time awake after sleep onset by sleep diary and polysomnography). For example, the percentage reductions of time awake after sleep onset was highest for the combined condition (63.5%), followed by cognitive-behavior therapy (55%), pharmacotherapy (46.5%), and placebo (16.9%). Subjects treated with behavior therapy sustained their clinical gains at follow-up, whereas those treated with drug therapy alone did not. Long-term outcome of the combined intervention was more variable. Behavioral treatment, singly or combined, was rated by subjects, significant others, and clinicians as more effective than drug therapy alone. Subjects were also more satisfied with the behavioral approach. CONCLUSIONS: Behavioral and pharmacological approaches are effective for the short-term management of insomnia in late life; sleep improvements are better sustained over time with behavioral treatment.

Aged↗
PubMed1999

Effect of pretransplantation ursodeoxycholic acid therapy on the outcome of liver transplantation in patients with primary biliary cirrhosis.

As ursodeoxycholic acid (UDCA) delays the need for transplantation, this could result in patients with more comorbid disease, therefore more likely to have a worse outcome posttransplantation. The aim of this study is to compare posttransplantation outcome in patients who received UDCA versus placebo who subsequently required a liver transplant. Data on all trial patients referred for transplantation were retrospectively collected from three randomized controlled trials of UDCA in patients with primary biliary cirrhosis (PBC). An intent-to-treat analysis was conducted with patients assigned to their original treatment allocation. UDCA and placebo groups were compared at trial entry, transplant referral, just before transplantation, and 1 month and 1 year posttransplantation. From 1987 to 1996, 37 UDCA-treated and 53 placebo patients were referred for transplantation; their age, sex, and serum bilirubin levels were similar at study entry. Immediately before transplantation, these two groups were again similar with respect to age, bilirubin level, Mayo risk score, and serum creatinine level. Posttransplantation survival rates at 1 month were 93.9% in the UDCA group and 88.4% in the placebo group, and 1 year survival rates were 90.3% and 78.4%, respectively (not significant). Posttransplantation, the two groups had similar rates of infection (53.9% v 58%); however, rejection occurred significantly less often in the UDCA group; 42.9% versus 68. 8% in the placebo group (P =.04). The posttransplantation outcome of UDCA-treated patients with PBC is no different from those who were administered placebo. There is no evidence to suggest the beneficial effect of UDCA in delaying the need for transplantation is associated with a worse outcome once liver transplantation becomes necessary.

Age Factors↗
PubMed1999

Initiating mechanisms involved in the pathobiology of traumatically induced axonal injury and interventions targeted at blunting their progression.

To gain better insight into the initiating factors involved in traumatically induced axonal injury cats and rats were subjected to various forms of traumatic brain injury. Following injury at intervals ranging from 10 min. to 3 hours, the animals were sacrificed and prepared in accordance with multiple immunocytochemical strategies capable of detecting focal changes in the axolemma, the subaxolemmal spectrin network, the underlying cytoskeleton as well as any related abnormalities in axoplasmic transport. Through these approaches it was recognized that the most severe forms of injury resulted in focal abnormalities of axonal permeability which were observed together with calpain-mediated spectrin proteolysis in the subaxolemmal network. These events were associated with compaction of the underlying neurofilaments and some microtubular loss which occurred without any direct evidence of overt axoplasmic proteolysis with the exception of the most severely injured fibers. In addition to these severely injured axonal profiles, other injured axons did not manifest overt changes in axolemmal permeability or early calpain-mediated spectrin proteolysis but demonstrated dramatic neurofilament and microtubular misalignment and impaired axoplasmic transport. Lastly, other small caliber axons showed another form of intraaxonal change manifested in the local pooling of organelles in the nodal and paranodal regions, with the suggestion that some of these changes may be reversible. In relation to these axonal responses the efficacy of various therapeutic investigations were assessed. The use of calcium chelators showed a trend for protection in those axons manifesting altered axolemmal permeability. However, the use of early and delayed hypothermia demonstrated dramatic protection resulting in significant reduction in the number of damaged axonal profiles. These studies illustrate the diversity and complexity of those axonal responses evoked by traumatic brain injury, suggesting that multiple forms of therapy may be needed to blunt these multifaceted forms of progression.

Animals↗
PubMed1999

MRI in 3-methylglutaconic aciduria type 1.

MRI in a young child with 3-methylglutaconic aciduria type 1 showed signal abnormalities in the basal ganglia which progressed despite successful treatment.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Genetic amniocentesis after multifetal pregnancy reduction.

OBJECTIVE: Our purpose was to evaluate the pregnancy loss rate resulting from genetic amniocentesis after multifetal pregnancy reduction. STUDY DESIGN: A cohort study was performed in pregnancies with maternal age >30 years. Pregnancy loss in a study population of 127 patients who underwent genetic amniocentesis after multifetal pregnancy reduction were compared with a control group of 167 patients who did not have genetic amniocentesis after multifetal pregnancy reduction. RESULTS: The pregnancy loss rate in patients who underwent genetic amniocentesis after multifetal pregnancy reduction was 3.1% (4/127 cases) compared with 7.2% (12/167 cases) in the controls (P >.05). In the study group evidence of infection was found in only 1 case, in which the pregnancy loss occurred 1 day after the amniocentesis. In the other cases the pregnancy losses occurred 5 weeks after genetic amniocentesis, and these losses could not be directly attributed to either genetic amniocentesis or the multifetal reduction procedure. CONCLUSION: Our data suggest that the performance of genetic amniocentesis after multifetal pregnancy reduction does not increase the risk of pregnancy loss over that observed in association with the reduction itself.

Adult↗
PubMed1999

Selective termination for structural, chromosomal, and mendelian anomalies: international experience.

OBJECTIVE: Our purpose was to evaluate the outcomes of selective termination for fetal anomalies at 8 centers with the largest known experiences worldwide. STUDY DESIGN: Outcomes in 402 cases of selective termination in pregnancies with dizygotic twins from 8 centers in 4 countries were analyzed by year, gestational age at procedure, and indication. Reductions of fetuses were as follows: 2 to 1, n = 345; 3 to 2, 39; >/=4 to 2 or 3, n = 18. Potassium chloride was used in all procedures. RESULTS: Selective termination resulted in delivery of a viable infant or infants in >90% of cases. Loss up to 24 weeks occurred in 7.1% of cases in which the final result was a singleton fetus and in 13.0% of cases in which the final result was twins. Loss was 6.6% as a result of structural abnormalities, 7.0% for chromosomal abnormalities, and 10% for mendelian abnormalities (difference not statistically significant). Loss rates for procedures were as follows: 9-12 weeks, 5.4%; 13-18 weeks, 8.7%; 19-24 weeks, 6.8%; and >/=25 weeks, 9.1% (difference not statistically significant). Mean gestational age at delivery was 35.7 weeks. No differences were seen in outcomes by maternal age. The rate of very early premature deliveries has fallen in recent years. There were no known cases of disseminated intravascular coagulation or serious maternal complications. CONCLUSION: (1) Selective termination, in the most experienced hands, can be technically performed in all 3 trimesters with good outcomes in >90% of cases. (2) The previously observed increase in second- versus first-trimester losses has diminished. (3) Third-trimester procedures, where legal, can be performed with a good outcome for the surviving fetus.

Chromosome Aberrations↗
PubMed1999

Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: the value of oxygen supplementation.

PURPOSE: To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions. METHODS: Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase. RESULTS: Results from the two animals kept in normoxia after retinal detachment confirmed previous reports that detachment caused the proliferation of Muller cells, the hypertrophy of Muller cell processes, and the disruption of glutamate recycling by Muller cells. Oxygen supplementation during detachment reduced Muller cell proliferation and hypertrophy and reduced the abnormalities in the distributions of glutamate, GluR-2, and glutamine synthetase. CONCLUSIONS: Oxygen supplementation reduced the reaction of retinal Muller cells to retinal detachment, limiting their proliferation and helping to maintain their normal structure and function. In the clinical setting, oxygen supplementation between diagnosis and reattachment surgery may reduce the incidence and severity of glial-based complications, such as proliferative vitreoretinopathy.

Animals↗
PubMed1999

Limiting photoreceptor death and deconstruction during experimental retinal detachment: the value of oxygen supplementation.

PURPOSE: To assess the role of hypoxia in causing the death and deconstruction of photoreceptors in detached retinas and the effectiveness of supplemental oxygen in limiting such damage. METHODS: Retinal detachment was induced surgically in the right eye of each of 10 cats. The cats were allowed to survive surgery for 3 days. Two were kept for these 3 days in normoxia (room air, 21% oxygen) and eight in hyperoxia (70% oxygen). The retinas were examined for cell death by use of labels for normal and fragmenting DNA, with antibodies and a cone sheath-specific lectin to demonstrate the status of their inner and outer segments, the synaptic structures of the outer plexiform layer, and the distribution of basic fibroblast growth factor (bFGF) and with in situ hybridization to demonstrate bFGF mRNA. RESULTS: Retinal detachment without oxygen supplementation caused the death of some photoreceptors; the loss of cytochrome oxidase from the inner segments and the collapse of the outer segments of surviving photoreceptors; the loss of synaptophysin profiles from the outer plexiform layer; and the loss of bFGF protein from retinal neurons and neuroglia but not from retinal vessels. Oxygen supplementation (hyperoxia) during detachment mitigated all these changes, reducing photoreceptor death, maintaining the specialized structures of surviving photoreceptors, and stabilizing the bFGF within the retina. CONCLUSIONS: In experimental retinal detachment, hypoxia caused by the separation of outer retina from its normal source of nutrients is a factor in inducing the death and deconstruction of photoreceptors as well as in the loss of bFGF from the detached retina. Hyperoxia offered to human patients between diagnosis of retinal detachment and surgery may enhance the function of the reattached retina.

Animals↗
PubMed1999

Controversies in the intrapartum management of twin gestations.

Advances in reproductive endocrine technology have helped to make twin gestations commonplace; however, as this article suggests, many unanswered questions and areas of controversy about the intrapartum management of twin gestations remain. Continued research in this area and the performance of prospective studies will shed further light on many of these topics.

Delivery, Obstetric↗
PubMed1999

Registration of 3D cerebral vessels with 2D digital angiograms: clinical evaluation.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy and speed of a new, semiautomatic method of three-dimensional (3D)-two-dimensional (2D) vascular registration. This method should help guide endovascular procedures by allowing interpretation of each digital subtraction angiographic (DSA) image in terms of precreated, 3D vessel trees that contain "parent-child" connectivity information. MATERIALS AND METHODS: Connected, 3D vessel trees were created from segmented magnetic resonance (MR) angiograms. Eleven total DSA images were registered with such trees by using both our method and the current standard (manual registration). The accuracy of each method was compared by using repeated-measures analysis of variance with correction for heterogeneity of variance to evaluate separation of curve pairs on the view plane. Subjective clinical comparisons of the two registration methods were evaluated with the sign test. Registration times were evaluated for both methods and also as a function of the error in the initial estimate of MR angiographic position. RESULTS: The new registration method produced results that were numerically superior to those of manual registration (P < .001) and was subjectively judged to be as good as or better by clinical reviewers. Registration time with the new method was faster (P < .001). If the rotational error in the initial estimate of MR angiographic position is less than 10 degrees around each axis, the registration itself took only 1-2 minutes. CONCLUSION: This method is quicker than and produces results as good as or better than those of manual registration. This method should be able to calculate an initial registration matrix during endovascular embolization and adjust that matrix intermittently with registration updates provided by automatic tracking systems.

Angiography, Digital Subtraction↗
PubMed1999

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Age Factors↗