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Background: Auditory verbal hallucinations (AVH) are the most prevalent symptom in schizophrenia. They are associated with increased activation within the temporoparietal cortices and are refractory to pharmacological and psychological treatment in approximately 25% of patients. Low frequency repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex has been demonstrated to be effective in reducing AVH in some patients, although results have varied. The cortical mechanism by which rTMS exerts its effects remain unknown, although data from the motor system is suggestive of a local cortical inhibitory effect. We explored neuroimaging differences in healthy volunteers between application of a clinically utilized rTMS protocol and a sham rTMS equivalent when undertaking a prosodic auditory task., Method: Single-blind placebo controlled fMRI study of 24 healthy volunteers undertaking an auditory temporoparietal activation task, who received either right temporoparietal rTMS or sham RTMS., Results: The main effect of group was bilateral inferior parietal deactivation following real rTMS. An interaction of group and task type showed deactivation during real rTMS in the right superior temporal gyrus (STG), left thalamus, left postcentral gyrus and cerebellum. However, the left parietal lobe showed an increase in activation following right sided real rTMS, but this increase was specific to a non-linguistic, tone-sequence task., Conclusion: rTMS does cause local inhibitory effects, not only in the underlying region of application, but also in functionally connected cortical regions. However, there is also a related, task dependent, increase in activation within selected cortical areas in the contralateral hemisphere; these are likely to reflect compensatory mechanisms, and such cortical activation may in some cases contribute to, or retard, some of the therapeutic effects seen with rTMS.

Background: Wheat allergy is 1 of the most common food allergies in children, yet few data are available regarding its natural history., Objectives: To define the natural course of wheat allergy and identify factors that help predict outcome in a large referral population of children with wheat allergy., Methods: Patients were included in the study if they had a history of a symptomatic reaction to wheat and a positive wheat IgE test result. Clinical history, laboratory results, and final outcome were recorded for 103 patients who met the inclusion criteria. Resolution of wheat allergy was determined based on food challenge results. Kaplan-Meier survival curves were generated to depict resolution of wheat allergy., Results: Rates of resolution were 29% by 4 years, 56% by 8 years, and 65% by 12 years. Higher wheat IgE levels were associated with poorer outcomes. The peak wheat IgE level recorded was a useful predictor of persistent allergy (P < .001), although many children outgrew wheat allergy with even the highest levels of wheat IgE., Conclusion: The median age of resolution of wheat allergy is approximately 6 1/2 years in this population. In a significant minority of patients, wheat allergy persists into adolescence.

Background: Cystic fibrosis (CF) lung disease is the major cause of mortality in CF patients. Lung transplantation remains a valid therapeutic option. It is unknown whether CF patients receiving healthy lungs have an equal susceptibility to infections when compared with non-CF lung transplant patients. Herein we present the largest analyses to date of the post-operative infection profiles of 60 CF and 60 non-CF lung transplant patients., Methods: Bilateral allogeneic lung transplantations and post-transplant management were performed according to standard clinical procedures. Post-operative infections were diagnosed by conventional methods based on clinical symptoms and laboratory cultures., Results: Sixty CF lung-transplant patients developed 278 post-operative respiratory infections, from which 307 pathogens were isolated. Pseudomonas aeruginosa predominantly occupied 60.3%, followed by Mycobacteria spp (7.2%), Aspergillus spp (5.9%) and Staphylococcus spp (5.5%). However, 60 non-CF transplant patients had 154 respiratory infections with 165 pathogens isolated. Pseudomonas aeruginosa was noted in 38.2%, followed by Aspergillus spp (9.7%), Staphylococcus spp (9.7%) and Mycobacteria spp (9.1%). The CF group demonstrated a significantly higher frequency of Pseudomonas respiratory infections than the non-CF group. Interestingly, no significant differences were detected in any infections from other systems including blood, sinuses, skin, wounds, oral cavity, bowel, eyes, peritoneal cavity and urinary tract. Moreover, the CF lung transplant patients had significantly less time free from Pseudomonas infections., Conclusions: The normal lungs implanted into CF patients had significantly higher susceptibility to Pseudomonas infections than those into non-CF patients, suggesting that defective innate immunity outside the lungs contributes to CF lung pathogenesis.

Management of brachial plexus injuries is geared toward normalization of limb function, primarily through optimization of nerve regeneration and mechanical increase in elbow flexion and shoulder stabilization. Changes in the skeletal muscles and the osteous structures of the upper extremity are ongoing throughout the course of treatment, mandating continual assessment and aggressive rehabilitation. In patients who present too late for microsurgical intervention, irreversible changes take place in skeletal muscles, highlighting the importance of early referral. However, secondary procedures have been shown to be beneficial in older patients and in those whose primary procedures failed. Further advances in bionics and stem cell therapy may help replace the dynamic functional deficits of obstetric brachial plexus palsy.

Background: Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patients. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions., Objective: We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration., Design: To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. SETTING/SUBJECTS/INTERVENTIONS: A total of 459 strip-chart recordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals., Results: Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation., Conclusion: Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement.

A 43-year-old woman developed right frontal headache and decreased vision in her OD 14 months after treatment of an intracranial aneurysm by wrapping with cotton gauze. A junctional visual field defect was present, and an MRI revealed a contrast-enhancing mass involving the right optic nerve, lateral chiasm, optic tract, and cavernous sinus. Biopsy demonstrated a marked inflammatory reaction mixed with strands of birefringent cotton gauze. Despite treatment with high-dose corticosteroids, visual loss progressed to bilateral blindness. This is the 30th reported case of an intracranial inflammatory tumor developing from a gauze-wrapped aneurysm ("gauzoma" or "muslinoma") and the worst reported visual outcome. Most cases have occurred in women and involved the optic nerves or chiasm. Visual improvement has sometimes occurred after treatment with abscess drainage, debulking, and/or corticosteroids. A rare complication of aneurysm wrapping, gauzomas causing visual loss have been reported up to 54 months after surgery.

The individual cellular immune response to intracellular antigens is modeled by the highly polymorphic major histocompatibility complex (HLA) class I molecules. The epitopes presented and the T cell repertoire that recognizes them depend on the HLA constitution of the individual. Therefore, to monitor and to modify an individual's HLA class I-driven cellular immune response, it is necessary to know the HLA class I alleles of the person and the possible epitopes of the target antigen presented by those alleles. In particular, this is necessary in order to design peptide-based vaccines and immune therapies for the treatment of diseases caused by viruses, intracellular parasites or cancer, and to monitor the immune response during those treatments. We describe a new set of HLA-A, -B, and -C locus-specific primers for the polymerase chain reaction (PCR) amplification of the whole coding sequence of these genes from complementary DNA (cDNA). We describe their use for typing and for the production of a library of recombinant HLA class I genes. We discuss two downstream applications of this gene collection: production of soluble HLA molecules and discovery of new epitopes.

Objective: We hypothesized that an artificial neural network, interconnected computer elements capable of adaptation and learning, could accurately estimate pulmonary artery occlusion pressure from the pulsatile pulmonary artery waveform., Setting: University medical center., Subjects: Nineteen closed-chest dogs., Interventions: Pulmonary artery waveforms were digitally sampled before conventional measurements of pulmonary artery occlusion pressure under control conditions, during infusions of serotonin or histamine, or during volume loading. Individual beats were parsed or separated out. Pulmonary artery pressure, its first time derivative, and the beat duration were used as neural inputs. The neural network was trained by using 80% of all samples and tested on the remaining 20%. For comparison, the regression between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure was developed and tested using the same data sets. As a final test of generalizability, the neural network was trained on data obtained from 18 dogs and tested on data from the remaining dog in a round-robin fashion., Measurements and Main Results: The correlation coefficient between the pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure and measured pulmonary artery occlusion pressure was.75, whereas that for the neural network estimate of pulmonary artery occlusion pressure was.97 (p <.01 for difference between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure estimates). The pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure showed a bias of 0.097 mm Hg (limits of agreement -7.57 to 7.767 mm Hg), whereas the neural network estimate of pulmonary artery occlusion pressure showed a bias of -0.002 mm Hg (-2.592 to 2.588 mm Hg). There was no significant change in the bias of the neural network estimate over the range of values tested. In contrast, the bias for the pulmonary artery diastolic pressure estimate significantly increased with the increasing magnitude of the pulmonary artery occlusion pressure. During round-robin testing, the neural network estimate of pulmonary artery occlusion pressure showed suboptimal performance (correlation coefficient between estimated and measured pulmonary artery occlusion pressure.59)., Conclusions: A neural network can accurately estimate pulmonary artery occlusion pressure over a wide range of pulmonary artery occlusion pressure under conditions that alter pulmonary hemodynamics. We speculate that artificial neural networks could provide accurate, real-time estimates of pulmonary artery occlusion pressure in critically ill patients.

A primary care trust has found that managers value the provision of locum cover for staff to attend multidisciplinary workshops. Evaluation shows that GPs and other staff appreciate protected learning time. If funding can be secured, the workshops will be supplemented with protected learning time in practices.

Objective and Importance: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion., Clinical Presentation: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere., Intervention: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved., Conclusion: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.

Background: A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein., Methods: Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3'-azido-3'-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells., Results: Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40-50% inhibition) than to the erythropoietic progenitors (10-20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40-60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic litter-mates also showed a significant decrease (25%) in CFU-GM., Conclusion: Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment.

The election of the Labour government in May 1997 has seen the continuation of advanced market reforms intended to modernize the UK National Health Service (NHS). The planning and implementation of information systems and technology (IS/IT) following these structural changes is both widespread and significant. An information strategy for the NHS, published recently, is intended to provide an initial seven-year program of life-long electronic health records for everyone in the United Kingdom. This article explores the potential role of these systems in the specific provision of the new primary health care groups. It argues that, if primary care physicians adopt appropriate delivery channels and service packages and are proactive in the use of IS/IT, then the outcome will produce more patient choice, less nonattendance, and consequently improved primary health care provision.

Objective: Review applications of interventional magnetic resonance imaging and describe methods, procedures, and additional instrumentation for the magnetic resonance "operating theater." Describe advantages of magnetic resonance navigation for biopsies of head and neck tumors., Study Design: Patients with palpable and nonpalpable head and neck and cranial base tumors were recruited into the study. Patients underwent magnetic resonance-guided biopsy. Retrospective analysis of 21 patients was conducted., Methods: 0.5 Tesla superconducting open magnetic resonance imaging was used for navigation of the biopsy needle. Patient records and magnetic resonance images were reviewed. The type, size, and location of the lesions were tabulated. Type of anesthesia and monitoring method were analyzed. The histopathologic correlation was conducted in patients who required further surgeries or open surgical biopsies., Results: Twenty-two biopsies were carried out in the magnetic resonance suite. One patient required general anesthesia and the other biopsies were conducted under intravenous sedation. There was only one case of nonconcurrence in a patient with Wegener's granulomatosis of the posterior orbit. Overall, a 92% concurrence rate between image-directed fine-needle aspiration, open biopsy, and surgical therapy was encountered. No complications occurred., Conclusions: The use of interventional magnetic resonance imaging to assist with fine-needle aspiration core biopsy has made the biopsy procedure safer and more accurate. Potentially morbid and disfiguring surgeries have been avoided in some patients. Deeper lesions have been more easily approached, as the needle for biopsy is under constant magnetic resonance guidance. Improved visualization for critical structures allows safer performance of biopsies. The primary difficulties of open magnetic resonance imaging relate to the need for nonferromagnetic instrumentation and equipment and their high costs. An inverse relationship exists between the imaging quality and the "dead time" required to acquire images.

Interventional magnetic resonance imaging defines the intraoperative application of magnetic resonance imaging technology, permitting the surgeon to work in an open magnetic field. The application of this technology to pediatric neurosurgery allows precise intraoperative localization of pathology, real-time assessment of the anatomical consequences of surgical and anesthetic interventions, accountability of brain shifts, confirmation of the exact site of biopsy or completeness of lesion removal, and immediate identification of some intraoperative and early postoperative complications. We present the case of a young boy with a cystic left midbrain tumor who underwent interventional magnetic resonance imaging guided aspiration and biopsy to illustrate the surgical advantages of this technology.

This paper seeks to adopt an interpretive case analysis for the study of the development of a clinical information system within a UK hospital. An initial literature review is outlined, which draws attention to the distinction between formal-rational and interpretive perspectives on information technology impacts. A case study is presented where a number of issues are identified which suggest that formal systems analysis techniques do not reflect the organizational realities within the hospital. The paper concludes with a brief discussion of the concerns for systems development, and notes the value of an interpretive perspective in this respect.

Primary cardiac tumors are rare entities with a frequency between 0.0017% to 0.28%. We report a 53 year old male with a primary cardiac myofibroblastic sarcoma that presented with a hemorrhagic pericardial effusion. A review of the literature is presented with a brief discussion of the clinical presentation diagnosis and treatment of benign and malignant primary cardiac tumors.

Argues that by interpreting the semantic content of different actions, it will be possible to draw boundaries between those aspects of a system that can be computerized and those that will best serve the purpose if left alone. This will dissuade systems developers from being caught in the technology trap. The argument is conducted in the context of developing IT-based medical thesauri for drug use management.

Objective: Our goal was to prospectively compare dynamic CT (DCT) and spiral CT (SCT) for evaluating patients with suspected abnormalities of the glottic region and correlate the observed differences between the two techniques with phantom measurements., Materials and Methods: Thirty-one patients suspected of having laryngeal abnormalities underwent DCT and SCT. The studies were evaluated by two head and neck radiologists for lesion detection, visualization of the paraglottic fat planes (PGFPs), motion artifact, respiratory misregistration, and overall image quality. Slice sensitivity profile (SSP) and image noise were measured for DCT and SCT for the imaging parameters used in this study., Results: Artifacts due to motion and respiratory misregistration were reduced with SCT compared with DCT. Laryngeal abnormalities and the adjacent PGFPs were better visualized with DCT than SCT. With use of similar imaging parameters, SSP and image noise were both increased with SCT compared with DCT., Conclusion: SCT produces high quality images of the larynx with less motion and respiratory misregistration artifacts than DCT. DCT allows better visualization of lesions and subtle anatomic features of the glottic region. SCT may substitute for DCT in laryngeal imaging.

Our previous studies demonstrated TRH stimulation of TSH beta gene expression in rat pituitary cell cultures and GH3 tumor cells in a transient expression assay. To begin to characterize the gene-proximal elements of the pathways involved in TRH stimulation of TSH beta gene transcription, we examined the effects of factors that increase intracellular calcium concentration, [Ca2+]i, or activate protein kinase C on TSH beta promoter activity in transfected GH3 cells. TPA, a tumor-promoting phorbol ester, stimulated a dose-dependent increase in TSH beta promoter activity at 8 h similar to TRH (2-3-fold). TPA did stimulate protein kinase C activation without [Ca2+] mobilization. The calcium ionophore ionomycin increased cytoplasmic free [Ca2+] by stimulating both calcium influx and release from internal stores without affecting protein kinase C. Ionomycin also stimulated a dose-dependent increase (2-fold) in TSH beta promoter activity at 8 h. However, the voltage-dependent Ca2+ channel agonist Bay K 8644, which increased influx of extracellular calcium, had little or no effect on TSH beta gene expression until 48 h (5-fold). Similar effects on prolactin/mRNA levels were observed in these cells. Effects of these factors were not additive, suggesting a common pathway(s) to stimulate gene expression. Inhibition of intracellular calcium mobilization by treatment with 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) inhibited ionomycin effects on gene expression without affecting phorbol ester activity, and, conversely, inhibition of protein kinase C activity by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) or TPA desensitization blocked TPA effects without affecting ionomycin activity.(ABSTRACT TRUNCATED AT 250 WORDS)