Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

[Modified McPeek score in multiple trauma patients. Prospective evaluation of a points system for recording follow-up factors]. / Modifiziertes McPeek-Punkte-System bei Polytraumapatienten. Prospektive Evaluierung eines Punktesystems zur Erfassung von Verlaufsfaktoren.

BACKGROUND: Many commonly available trauma scores predict mortality, but to evaluate the success of a certain therapy or for difficult scientific and epidemiological purposes this may be insufficient in the face of improved survival rates. For outcome analysis of multiple trauma patients, the extent of medical resources needed could be an additional outcome measurement. McPeek et al. developed a potential scoring system for elective surgery patients, which was recently modified for multiple trauma patients. AIM: The current study investigated if the McPeek score could be prospectively used in multiple trauma patients and whether it could become an additional helpful tool in outcome assessment. Applicability was assessed by practical examples. MATERIAL AND METHODS: In this prospective single-centre study at the University Hospital of Innsbruck, Austria, between December 2008 and November 2010 multiple trauma patients (≥ 18 years) with an injury severity score (ISS) ≥ 17 were enrolled. Besides demographic data, prehospital vital parameters and diagnoses, all diagnoses from the trauma, mortality, length of stay in the intensive care unit and the hospital were recorded. The commonly used trauma scores ISS, revised trauma score (RTS), a severity characterization of trauma (ASCOT) and trauma and injury severity score (TRISS) were applied and an observed McPeek score was allocated following end of hospitalization. The McPeek scoring system was used according to the latest modifications. A correlation between trauma scores and the McPeek score was performed. The McPeek score was then predicted by a common trauma score using ordinal regression with the polytomous universal model (PLUM method). By subtracting the predicted from the observed McPeek scores the residual McPeek value was calculated and used for practical examples of outcome analysis with the McPeek scoring system. RESULTS: Out of 406 identified multiple trauma patients during the study phase, 183 had to be excluded due to missing data (mainly prehospital or following transfer). A total of 223 patients (mean ISS 31.2, mean age 47.2 years) were enrolled and assigned to the population-based observed McPeek score (median 4.0). Correlation coefficients were Glasgow coma scale (GCS) 0.59, ISS 0.62, RTS 0.65, TRISS 0.74 and ASCOT 0.77 (p < 0.0001). The TRISS predicted the McPeek score best in ordinal regression (pseudo-R(2) = 0.944, p < 0.0001). The residual McPeek score (observed minus predicted) was used to illustrate the influence of the blood glucose level on admission and the influence of head injury on outcome of multiple injury patients in detail. CONCLUSION: The modified McPeek score is applicable to multiple trauma patients to assess outcome for scientific or epidemiological purposes. Its main advantage is that it quantifies outcome independently of regional or national circumstances.

[Multilocular Paget's disease in IBMPFD syndrome. A case report with 14-year follow-up]. / Multilokulärer Morbus Paget bei IBMPFD-Syndrom. Darstellung eines Krankheitsverlaufes über 14 Jahre.

Paget's osteodystrophia deformans is a monoostotic or polyostotic disease of the skeletal system with increased bone remodelling, structural modifications and skeletal deformation, typically arranged like a chessboard. The unusual case of a patient is described who had suffered from generalized Paget's disease of the bone for 14 years and also developed progressive myopathy and a behavioural variant frontotemporal dementia. Further cytogenetic diagnostics revealed a point mutation in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 consistent with the finding of inclusion body myopathy with early onset Paget's disease and frontotemporal dementia (IBMPFD syndrome). A causal therapy of this disease is not known. Conservative treatment with bisphosphonate therapy, intensive physiotherapeutic exercise and psychotherapeutic treatment was performed to retard the progression of the disease.

[Recurrent synovial chondromatosis of the tarsometatarsal joint. Case report and review of literature]. / Rezidivierende synoviale Chondromatose im Tarsometatarsalgelenk. Fallbericht und Literaturübersicht.

Primary synovial chondromatosis is a rare and usually monoarticular metaplasia of the synovia. It may recur, but the tendency to malignant transformation is very low. The radiological and histopathological differentiation from low grade chondrosarcoma can be difficult. We present a case report of a 32-year-old male with synovial chondromatosis in the tarsometatarsal joint area, which is an uncommon localization.

Cortisol levels predict motion sickness tolerance in women but not in men.

A variety of intrinsic and extrinsic factors contribute to motion sickness severity in a stressful motion environment. The interplay of all these factors may partially explain the high inter-subject variability of motion sickness susceptibility found in many studies as well as some of the contradictory findings between studies regarding the modulating influence of single factors. We investigated the role of endogenous cortisol levels, gender and repetitive experience for motion sickness susceptibility. Motion sickness was induced in 32 healthy, but motion-sickness susceptible volunteers (16:16 males:females), by means of a vection drum. Subjects were investigated between 8:00 am (high cortisol) and 11:00 am (low cortisol), and on five consecutive days. Tolerance to rotation (RT) of the drum, motion sickness symptom ratings (SR) and salivary cortisol levels were assessed. Baseline cortisol levels correlated positively with RT in women, but not in men. RT showed a gender-specific time course across days, with higher values in males than in females on day 1, and sensitization on day 3 only in men. SR and cortisol levels following rotation did not differ between males and females, or between testing days. Gender differences in motion sickness susceptibility appear to be linked to a different role of basal cortisol levels for motion sickness tolerance. Results clearly indicate the need to control for gender, day time and cortisol levels in studies of motion sickness.

Clinical significance and neuropathology of primary MADD in C34-T and G468-T mutations of the AMPD1 gene.

OBJECTIVE: Primary myoadenylate deaminase deficiency (MADD) is probably the most frequent inborn metabolic myopathy with a prevalence of up to 2%. It is the result of mutations in the AMPDI gene, the most common of which is a C34-T transition in exon 2. The importance of the more rare mutation G468-T in exon 5 is uncertain. Primary objective was to elucidate the clinical significance of the enzyme disorder, which remains unclear since its first description in 1978. We further examined the existence of an association of MADD with other muscle disorders, such as malignant hyperthermia and rhabdomyolysis, as was suspected in earlier studies. MATERIAL AND METHODS: In a large collection of 1673 muscle biopsies that had been stored deep frozen we identified 33 cases of primary MADD, 12 of which without any other coinciding muscle diseases, by histochemical, biochemical and molecular genetic examinations. Clinical and laboratory data was collected. By additional examination of randomly chosen blood samples we identified one person carrying the rare compound heterozygosity C34-T/ G468-T, who was examined in clinical respects and a muscle biopsy was taken. RESULTS: As underlying mutation, the most common transition C34-T/C 143-T was detected in 33 cases. One patient carried the compound heterozygosity C34-T/G468-T. The overall frequency of MADD in the contingent was 1.8%. Only three patients out of 12 with isolated primary MADD suffered from muscle complaints, one of whom did not experience the typical symptoms of exercise related myalgia, muscle cramps and weakness as described by Fishbein. The patient carrying C34-T/G468-T was a fully healthy female. She had never experienced any muscle complaints. Any association with other neuromuscular disorders, if not completely ruled out, was found to be very unlikely. CONCLUSION: The results suggest that MADD itself is unlikely to be solely responsible for the manifestation of muscular symptoms. It is probable that either the loss of a compensation mechanism or coexistent disturbances in muscle metabolism which are unidentified so far are required for the emergence of complaints.

Regulation of integrin function by T cell activation: points of convergence and divergence.

Lymphocyte adhesiveness is dynamically regulated in response to conditions in the extracellular environment. One mechanism of regulation of integrin adhesion receptors involves a rapid, but transient, increase in integrin function upon T lymphocyte activation. These integrin activating signals can be initiated either via ligation of Ig superfamily members that are coupled to tyrosine kinase cascades, such as the CD3/T cell receptor, CD2, and CD28, or by G protein-coupled receptors for chemokines. Analysis of integrin activation induced by CD3/TCR, CD2 and CD28 suggests a critical role for phosphoinositide 3-OH kinase (PI 3-K). This review summarizes recent insights into PI 3-K-dependent regulation of integrin function in leukocytes, including the mechanisms by which these receptors are coupled to PI 3-K, and potential downstream effectors of PI 3-K that regulate integrin-mediated adhesion in leukocytes.

Simple, inexpensive computerized rodent activity meters.

We describe two approaches for using obsolescent computers, either an IBM PC XT or an Apple Macintosh Plus, to accurately quantify spontaneous rodent activity, as revealed by continuous monitoring of the spontaneous usage of running activity wheels. Because such computers can commonly be obtained at little or no expense, and other commonly available materials and inexpensive parts can be used, these meters can be built quite economically. Construction of these meters requires no specialized electronics expertise, and their software requirements are simple. The computer interfaces are potentially of general interest, as they could also be used for monitoring a variety of events in a research setting.

Gross-total surgery of supratentorial low-grade gliomas under intraoperative MR guidance.

BACKGROUND AND PURPOSE: Length of survival of patients with low-grade glioma correlates with the extent of tumor resection. These tumors, however, are difficult to distinguish intraoperatively from normal brain tissue, often leading to incomplete resection. Our goal was to evaluate the effectiveness of intraoperative MR guidance in achieving gross-total resection. METHODS: We studied 12 patients with low-grade glioma who underwent surgery within a vertically open 0.5-T MR system. During surgery, localization of residual tumor tissue was guided by interactive, near real-time imaging. The amount of residual tumor tissue on MR images was evaluated at the point of the operation at which the neurosurgeon would have terminated the procedure under conventional conditions (first control) and again before closing the craniotomy. RESULTS: Significant residual tumor (more than 10% of original tumor volume) was shown in eight patients at the first control condition. The percentage of resection varied from 26% to 100% (mean, 68%) at this time. Twelve tissue samples from seven patients were obtained in areas identified as residual tumor on MR images. In 10 cases, the neuropathologic investigation confirmed the presence of residual low-grade glioma; in two cases, the borderzone of tumor was identified. In evaluating the final sets of images, we found total resection in six cases, over 90% resection in five cases, and 85% resection in one case (mean, 96%). CONCLUSION: Surgical treatment of low-grade gliomas under intraoperative MR guidance provides improved resection results with maximal patient safety.

Intradiploic arachnoid cyst with extensive deformation of craniofacial osseous structures: case report.

OBJECTIVE AND IMPORTANCE: A unique case of a large intradiploic arachnoid cyst involving craniofacial osseous structures is reported. CLINICAL PRESENTATION: The patient presented with a hard mass in the right frontal region, proptosis, and inferior globe displacement. Computed tomography revealed an intraosseous cyst of cerebrospinal fluid intensity with extension from the anterior cranial fossa to the infratemporal fossa. INTERVENTION: After resection of the cyst wall and closure of two small round dural defects, the involved craniofacial region was reconstructed. CONCLUSION: The medical history of the patient and the intraoperative observations support the contention that the cyst in the reported case was congenital in origin. The features concerned with diagnosis and pathogenesis of this rare entity are discussed.

Pulmonary nocardiosis with cutaneous involvement mimicking a metastasizing lung carcinoma in a patient with chronic myelogenous leukaemia.

We report a unique case of a man suffering from chronic myelogenous leukaemia who presented with clinical symptoms, X-ray, and bronchoscopical findings consistant with a bronchopulmonary space-occupying process which was suspected to be a central lung carcinoma as a secondary de novo malignancy. In addition, the patient developed several subcutaneous nodular livid red lesions on the left forearm which were considered to be cutaneous metastases of the presumptive lung malignancy. Treatment was started with percutaneous radiation of the mediastinum over a period of ten days with a total dose of 25 Gray. The patient died from circulatory and respiratory failure. Only post mortem pathological examination was indicative of a nocardiosis of the lungs with haematological spread to eosophagus, pleura, and subcutaneous skin of the left forearm. Unfortunately, diagnosis of nocardiosis could not finally proven by culture or molecular biological methods. A lung carcinoma or an infiltrate of residual or relapsing chronic myelogenous leukemia in the lung could be definitely ruled out.

[Unusual suicide by gunshot wound to the head with a signal pistol]. / Ungewöhnlicher Suizid durch Kopfschuss mit einer Signalpistole.

The professional access to weapons plays a role in the choice of suicide instruments. Light and signalling ammunition is used by police forces, in the military, in sports, and professional navigation. An unusual suicide of a shipowner by means of a signal-pistol is presented. The signal cartridge was shot into the head. Penetrating the skull the cartridge entered the brain. The burning-out of the signal-set--taking about 10 seconds--initiated a flat-burning.--This case shows once more the dangerous misuse of light and signal ammunition.

[Type and extent of preoperative imaging before radical prostatectomy]. / Evaluation von Art und Ausmass der präoperativen Bildgebung vor radikaler Prostatektomie.

BACKGROUND: According to current guidelines, in cases of newly diagnosed prostate cancer the type and extent of imaging to be performed should be based on the patient's risk profile. We investigated the rate of computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy carried out before radical prostatectomy (RP) depending on the individual risk profile. PATIENTS AND METHOD: Between 1 January 2006 and 31 December 2007, a total of 1,018 consecutive patients who had not received neoadjuvant hormone therapy were treated with RP in our department. We determined the preoperative rates of CT, MRI, and bone scintigraphy by reviewing the medical charts. The patients were stratified according to the D'Amico criteria into low-risk, intermediate-risk, and high-risk groups. RESULTS: Of the 1,018 subjects, 493 (48%) were classified as low-risk, 403 (40%) as intermediate-risk, and 122 (12%) as high-risk patients, respectively. The rate of preoperative abdominal CT/MRI and bone scintigraphy was 17 and 23% in the low-risk group, 25 and 39% in the intermediate-risk patients, and 39 and 57% in the high-risk group. CONCLUSION: The rate of preoperative CT and bone scintigraphy is extremely high in the low-risk group. In contrast the rate in the high-risk patients more likely appears to be too low. The discrepancy between the rates of preoperative imaging subject to the patient's risk profile shows that precisely formulated guidelines addressing this issue are needed.

[Atypical metastasis of stomach carcinoma]. / Atypische Metastasierung eines Magenkarzinoms.

We report a case of unusual metastases from a gastric cancer. In a 66 years old female with bone metastases a breast cancer was diagnosed. The patient was treated by ablative surgery and chemotherapy but died short time later. An autopsy was performed and showed a large signetring cell carcinoma of the stomach. Further a diffuse involvement of the spleen unknown until autopsy was diagnosed. Serial tissue sections of all metastatic localizations were made. Histopathology and immunostaining including oestroprogesterone receptors identified a gastric cancer as the primary malignancy. A review of the recent literature on breast metastases from gastrointestinal tumours, gastric metastases from breast cancer and the problem of second primary malignancies is given. Further we reviewed the occult metastatic spread of the spleen and the importance of splenectomy in case of total gastrectomy.

[Acute blindness caused by fungal infection in chronic myeloid leukemia]. / Akute Erblindung durch Pilzinfektion bei chronisch myeloischer Leukämie.

PATIENT: A 35-year-old man had suffered from leukemia since September 1990. A transplantation of bone marrow was carried out in February 1994. He developed a graft-versus-host disease in November 1995. In December 1995 a keratoplasty was necessary because of a perforated corneal ulcer. 17 days later the patient noted a complete loss of vision, first in the left and one day later in the right eye. The optic nerve head was white and the retina looked ischaemic like in central retinal artery occlusion. A hypodensic area was found in the frontal brain reaching up to the optic chiasm in computer tomography. Inspite of intensive treatment the immunosuppressed patient died 4 days after he had become blind. Autopsy showed a mycotic infiltration by mucormycosis of the brain and the right optic nerve sheath. This human- pathogenic fungal infection belongs to the group of mould as well as aspergillus. CONCLUSION: Mycosis should be considered in the differential diagnosis of acute visual loss in immunosuppressed patients.

[Pulsatile tinnitus. Causes, diagnostic procedures, case presentation]. / Pulsatiler Tinnitus. Ursachen, diagnostisches Vorgehen, Falldarstellung.

The pulsatile tinnitus is a rare sign. It is characterised by a rhythmic sound that is synchronous with the patient's heart beat. The underlying causes vary widely and may be life-threatening. Pulsatile tinnitus may be due to cardiac or vascular malformation, metabolic disorders, hyperdynamic circulatory states, elevated intracranial pressure, and tumours. The diagnostic evaluation includes physical examination, audiologic assessment and often computed image processing for precise topodiagnosis. A case report illustrates our current management of patients with pulsatile tinnitus.

The Peyer's patch microenvironment suppresses T cell responses to chemokines and other stimuli.

Immunosurveillance of mucosal sites presents immune cells with challenges not encountered in the periphery. T cells in the gut must distinguish enteric pathogens from innocuous non-self Ag derived from food or commensal bacteria. The mechanisms that regulate T cells in the gut remain incompletely understood. We assessed the effect of the Peyer's patch microenvironment on T cell responses to chemokines. Chemokines are believed to play an important role during T cell priming by facilitating T cell migration into and within lymphoid tissues as well as T cell encounter and interaction with APCs. We found a profound suppression of chemokine-stimulated T cell chemotaxis and actin polymerization in Peyer's patch relative to lymph node. Chemokine hyporesponsiveness is imposed upon T cells within hours of their entry into Peyer's patches and is reversed following their removal. Suppression was not restricted to chemokine stimulation, as T cell responses to Con A and PMA were also suppressed. The global nature of this defect is further underscored by an impairment in calcium mobilization. Evidence indicates that a soluble factor contributes to this hyporesponsiveness, and comparison of Peyer's patches and lymph nodes revealed striking differences in their chemokine and cytokine constitution, indicating a marked Th2 bias in the Peyer's patches. The role of the Th2 microenvironment in mediating suppression is suggested by the ability of Nippostrongylus brasiliensis to elicit hyporesponsiveness in lymph node T cells. The suppressive milieu encountered by T cells in Peyer's patches may be critical for discouraging undesired immune responses and promoting tolerance.

Reliability of Medicaid claims files for use in psychiatric diagnoses and service delivery.

To investigate the reliability of Medicaid claims data for use in research, clinical decision-making, and policy, medical records were abstracted of 105 inpatient stays on the psychiatric service of a large general hospital. Primary and secondary diagnoses and outpatient specialty mental health services after hospitalization were compared between Medicaid claims data and medical record information. Primary and secondary diagnoses were reliable, but claims data failed to capture several types of outpatient services. This suggests strategies to use claims files more appropriately.

Cerebellopontine angle lipoma: case report and review of the literature.

Intracranial lipomas located in the cerebellopontine angle are extremely rare. These tumours are mal-developmental lesions which can cause slowly progressive neurological symptoms. The clinical management of these tumours differs significantly from other lesions in this region. A 27 year old woman presented with a 2-month history of vertigo and a slowly progressive deterioration of hearing in the left ear. Computed tomography (CT) revealed a large low-density mass in the left cerebellopontine angle without any contrast-enhancement. In T1-weighted magnetic resonance imaging (MRI) the lesion was hyper-intense and did not enhance after application of gadolinium. Areas of lower signal intensity inside of the lesion were suggested as incorporated cranial nerves. A left retro-sigmoidal approach in a semi-sitting position was chosen to expose the tumour. After reducing the tumour mass, the tumour was dissected from the cranial nerves which were incorporated into the tumour. The residual tumour was adherent to the brain stem and the encased lower cranial nerves, allowing only a near subtotal resection of the highly vascularized tumour in order to avoid neurological deficits. The histological examination revealed a lipoma. Attempts at complete removal of cerebellopontine angle lipomas usually result in severe neurological deficits. Conservative treatment should therefore be preferred. Limited surgery is indicated if the patients suffer from disabling neurological symptoms and signs e.g., vertigo, nausea, trigeminal neuralgia, facial weakness or facial spasm.