High-level disinfection of re-usable neonatal resuscitation equipment through boiling and steaming.

Infection and asphyxia are two major causes of neonatal death globally. Where single-use resuscitation devices or sterilization of re-usable devices are unavailable, there is a need for effective, low-cost methods of high-level disinfection. Laboratory validation examined the efficacy of boiling and enclosed steaming (without pressure) as methods for attaining high-level disinfection of re-usable neonatal resuscitation equipment. The microbial load extracted and measured for each test article met internationally accepted standards for high-level disinfection. Boiling and steaming are low-cost, effective methods for reprocessing re-usable neonatal resuscitation devices in low- and middle-income countries.

Spinal Stenosis in Familial Transthyretin Amyloidosis.

Here we describe a patient with genetically confirmed ATTR, a family history of the disease and histological confirmation following carpal tunnel release surgery but no other manifestations. The first major neurological or systemic manifestation was cauda equina syndrome with ATTR deposits contributing to lumbar spinal stenosis. Recent gene therapy trials showed improvement in the neuropathy in TTR amyloidosis. This case highlights the need for awareness of the heterogeneous neurological phenotype seen in ATTR to aid earlier diagnosis especially now that disease modifying therapies are available.

Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient.

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear.

Renal transplantation in systemic amyloidosis-importance of amyloid fibril type and precursor protein abundance.

Renal transplantation remains contentious in patients with systemic amyloidosis due to the risk of graft loss from recurrent amyloid and progressive disease. Outcomes were sought among all patients attending the UK National Amyloidosis Centre who received a renal transplant (RTx) between January 1978 and May 2011. A total of 111 RTx were performed in 104 patients. Eighty-nine percent of patients with end-stage renal disease (ESRD) due to hereditary lysozyme and apolipoprotein A-I amyloidosis received a RTx. Outcomes following RTx were generally excellent in these diseases, reflecting their slow natural history; median graft survival was 13.1 years. Only 20% of patients with ESRD due to AA, AL and fibrinogen amyloidosis received a RTx. Median graft survival was 10.3, 5.8 and 7.3 years in these diseases respectively, and outcomes were influenced by fibril precursor protein supply. Patient survival in AL amyloidosis was 8.9 years among those who had achieved at least a partial clonal response compared to 5.2 years among those who had no response (p = 0.02). Post-RTx chemotherapy was administered successfully to four AL patients. RTx outcome is influenced by amyloid type. Suppression of the fibril precursor protein is desirable in the amyloidoses that have a rapid natural history.

Hereditary lysozyme amyloidosis -- phenotypic heterogeneity and the role of solid organ transplantation.

OBJECTIVES: Lysozyme amyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation. DESIGN: Retrospective evaluation of patients with ALys. SETTING: UK National Amyloidosis Centre. PATIENTS: All 16 patients with ALys followed at the centre. RESULTS: A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx. CONCLUSIONS: Lysozyme amyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival.

Solid organ transplantation in AL amyloidosis.

Vital organ failure remains common in AL amyloidosis. Solid organ transplantation is contentious because of the multisystem nature of this disease and risk of recurrence in the graft. We report outcome among all AL patients evaluated at the UK National Amyloidosis Centre who received solid organ transplants between 1984 and 2009. Renal, cardiac and liver transplants were performed in 22, 14 and 9 patients respectively, representing <2% of all AL patients assessed during the period. One and 5-year patient survival was 95% and 67% among kidney recipients, 86% and 45% among heart recipients and 33% and 22% among liver recipients. No renal graft failed due to recurrent amyloid during median (range) follow up of 4.8 (0.2-13.3) years. Median patient survival was 9.7 years among 8/14 cardiac transplant recipients who underwent subsequent stem cell transplantation (SCT) and 3.4 years in six patients who did not undergo SCT (p = 0.01). Amyloid was widespread in all liver transplant recipients. Solid organ transplantation has rarely been performed in AL amyloidosis, but these findings demonstrate feasibility and support a role in selected patients.

[Anatomic pathology workflow. IHE: modeling based on current developments in HL7 and DICOM]. / Der Workflow in der Pathologie. IHE: Modellierung unter Berücksichtigung der aktuellen Entwicklungen in HL7 und DICOM.

AIMS: Consistent and complete information is essential for medical decision making. Anatomic pathology as a diagnostic discipline has a central role in the exchange of information between clinical departments throughout the diagnostic process. The IHE (Integrating the Healthcare Enterprise) has created an integration profile for information systems based on HL7 and DICOM standards. METHODS: Created by the IHE Anatomic Pathology working group, the integration profile (so-called Technical Framework) ensures the consistent management of data and material in the pathology laboratory information system (PLIS). HL7 and DICOM standards are taken into account. Communication processes both within and outside the institute are modelled using eight actors and 13 transactions. RESULTS: The IHE's Technical Framework covers basic business processes, provision of diagnostic services and includes requesting examinations, as well as image and report management. In particular, a consistent data model for incoming material, containers, cartridges and slides has been developed and approved by the standards committee.

CNS metastases of carcinoma ex pleomorphic adenoma of the parotid gland.

Pleomorphic adenomas (PAs), also known as benign mixed tumors, are common tumors of the parotid gland. These tumors occasionally undergo malignant transformation, with potentially devastating consequences. This case report presents the clinical and radiographic features of a rare case of biopsy proved brain and spinal cord metastases arising from carcinoma ex PA of the parotid gland.

Organ transplantation in hereditary apolipoprotein AI amyloidosis.

Patients with hereditary apolipoprotein AI (apoAI) amyloidosis often have extensive visceral amyloid deposits, and many develop end-stage renal failure as young adults. Solid organ transplantation to replace failing organ function in systemic amyloidosis is controversial due to the multisystem and progressive nature of the disease and the risk of recurrence of amyloid in the graft. We report the outcome of solid organ transplantation, including dual transplants in 4 cases, among 10 patients with apoAI amyloidosis who were followed for a median (range) of 16 (4-28) and 9 (0.2-27) years from diagnosis of amyloidosis and transplantation, respectively. Eight of 10 patients were alive, seven with a functioning graft at censor. Two patients died, one of disseminated cytomegalovirus infection 2 months after renal transplantation and the other of multisystem failure following severe trauma more than 13 years after renal transplantation. The renal transplant of one patient failed due to recurrence of amyloid after 25 years. Amyloid disease progression was very slow and the natural history of the condition was favorably altered in both cases in which the liver was transplanted. Failing organs in hereditary apoAI amyloidosis should be replaced since graft survival is excellent and confers substantial survival benefit.

Microarray data mining using gene ontology.

DNA microarray technology allows scientists to study the expression of thousands of genes--potentially entire genomes--simultaneously. However the large number of genes, variety of statistical methods employed and the complexity of biologic systems complicate analysis of microarray results. We have developed a web based environment that simplifies the presentation of microarray results by combining microarray results processed for statistical significance with probe set annotation by Genbank, NCBI RefSeqs, GeneCards and the Gene Ontology. This allows rapid examination and classification of microarray experiments--annotated by NCIBI tools --by Statistical Significance and Gene Oncology Classes. By providing a simple, easily understood interface to large microarray data sets, this tool has been particularly useful for small research groups focused on a small number of related genes and for researchers who want to ask simple questions without the overhead of complex data management and analysis.

Diagnosis of amyloidosis by histological examination of subcutaneous fat sampled at the time of pacemaker implantation.

Atrioventricular conduction disease may occur in a range of conditions. If echocardiography suggests the presence of an infiltrative cardiomyopathy the diagnosis of amyloidosis may be confirmed by subcutaneous fat sampling from the site of pacemaker implantation. This technique requires no additional invasive procedure and confers no extra risk for the patient. Confirmation of amyloidosis provides important prognostic information and may allow specific treatment.

Unicentric Castleman's disease complicated by systemic AA amyloidosis: a curable disease.

BACKGROUND: Castleman's disease (angiofollicular lymph node hyperplasia) is a group of rare lymphoproliferative disorders sharing characteristic clinical and histological features, and usually accompanied by a marked systemic inflammatory response. All types may be complicated by acquired systemic amyloidosis, usually of AA type, but occasionally of AL type associated with monoclonal gammopathy. DESIGN: Descriptive study of five patients with unicentric Castleman's disease complicated by systemic AA amyloidosis. METHODS: A diagnosis of amyloidosis was confirmed by microscopy and immunohistochemical staining. Serum concentrations of C-reactive protein (CRP) and serum amyloid A protein (SAA) were measured by immunoassays. Radiolabelled serum amyloid P component scintigraphy was used to monitor the progress of amyloid deposition. RESULTS: In four patients the primary diagnosis was made only after years of investigation of systemic symptoms. The tumours were resected in all cases, leading to remission of the systemic inflammatory state. Long-term follow-up in four patients, including scintigraphy, showed regression of amyloid deposits. DISCUSSION: This rare but usually fatal condition can be cured surgically even in advanced cases. Awareness of the diagnosis and its correct management are important in investigation of patients with unexplained systemic symptoms, especially associated with systemic amyloidosis.

mu-Bis(diphenylphosphino)methane-P:P'-octacarbonyldimanganese(Mn-Mn) and its toluene hemisolvate.

The Mn-Mn bonds in the two independent molecules of the unsolvated title compound, [Mn(2)(C(25)H(22)P(2))(CO)(8)], (I), are 2.9714 (7) and 2.9746 (7) A. This bond is distinctly shortened in the toluene hemisolvate, [Mn(2)(C(25)H(22)P(2))(CO)(8)] x 0.5C(7)H(8), (II), to 2.9338 (14) A and this shortening is accompanied by an increase in magnitude of the P-Mn-Mn-P torsion angle [26.93 (3) and 28.44 (3) degrees in (I), and 33.25 (7) degrees in (II)], while the P...P 'bite' is much less affected [3.092 (2) and 3.099 (2) A in (I), and 3.091 (3) A in (II)]. The toluene solvate molecule in (II) lies on a twofold axis.

Prototype Web-based continuing medical education using FlashPix images.

Continuing Medical Education (CME) is a requirement among practicing physicians to promote continuous enhancement of clinical knowledge to reflect new developments in medical care. Previous research has harnessed the Web to disseminate complete pathology CME case studies including history, images, diagnoses, and discussions to the medical community. Users submit real-time diagnoses and receive instantaneous feedback, eliminating the need for hard copies of case material and case evaluation forms. This project extends the Web-based CME paradigm with the incorporation of multi-resolution FlashPix images and an intuitive, interactive user interface. The FlashPix file format combines a high-resolution version of an image with a hierarchy of several lower resolution copies, providing real-time magnification via a single image file. The Web interface was designed specifically to simulate microscopic analysis, using the latest Javascript, Java and Common Gateway Interface tools. As the project progresses to the evaluation stage, it is hoped that this active learning format will provide a practical and efficacious environment for continuing medical education with additional application potential in classroom demonstrations, proficiency testing, and telepathology. Using Microsoft Internet Explorer 4.0 and above, the working prototype Web-based CME environment is accessible at http://telepathology.upmc.edu/WebInterface/NewInterface/welcome.html.

Pathology imaging on the Web. Extending the role of the pathologist as educator to patients.

The increasing role of patients in medical decision making and the growing availability of medical information are changing the physician-patient relationship. One aspect of this change is that patients are searching for medical information on the Internet and are visiting sites, including pathology sites, that were not originally intended for patient use. This article describes evidence for this activity and how the University of Pittsburgh Medical Center Department of Pathology has evolved mechanisms to handle patient use of its web site.

Carotid artery tandem lesions: frequency of angiographic detection and consequences for endarterectomy.

BACKGROUND AND PURPOSE: Several prospective trials have shown that ischemic stroke can be prevented by performing an endarterectomy in patients with high-grade carotid stenosis. Our purpose was to ascertain the frequency of carotid artery tandem lesions and to determine whether their presence alters the surgeon's decision to perform an endarterectomy. METHODS: We retrospectively reviewed the cerebral angiograms obtained between January 1994 and June 1996 in 853 patients with carotid occlusive disease. Studies were analyzed for the presence of internal carotid artery (ICA) stenosis as well as for tandem lesions (defined as > or = 50% diameter stenosis) within the common carotid artery, carotid siphon, or proximal intracranial arteries. The frequency of intracranial saccular aneurysms was determined. RESULTS: Six hundred seventy-two of the 853 patients had a carotid bifurcation stenosis of 70% or greater or underwent an endarterectomy. Of these, a carotid siphon stenosis of 50% or greater was noted in 65 patients (9.7%) and was ipsilateral to an ICA stenosis in 37 patients (5.5%). A common carotid stenosis was present in 29 patients (4.3%), ipsilateral to an ICA stenosis in 14 patients (2.1%). A stenosis of 50% or greater within the proximal intracranial circulation was present in 28 patients (4.2%), ipsilateral to an ICA stenosis in 15 patients (2.2 %). Four patients had tandem stenoses at more than one site. Tandem stenoses in the siphon or intracranial segments were noted in 13.5% with a bifurcation stenosis and in 8.8% of those with no bifurcation stenosis. Endarterectomy was performed in 48 of the 66 patients with tandem stenotic lesions. CONCLUSION: The presence of a tandem lesion infrequently alters the surgeon's decision to perform an endarterectomy. However, the importance of detecting tandem stenoses cannot be underestimated, since they may have important implications for long-term medical management in symptomatic patients.

Continuing medical education on the World Wide Web (WWW). Interactive pathology case studies on the Internet.

OBJECTIVE: To present interactive online continuing medical education (CME) over the World Wide Web as a more efficient alternative to traditional modes of CME delivery. DESIGN: A departmental Web site available to those with access to the Internet. SETTING: A tertiary-care teaching hospital in the United States. RESULTS: Comprehensive case studies have been developed and are complete with images, text, and questions, including explanations for correct and incorrect responses. The images are linked to pertinent text to maximize their educational value. The cases are easily accessible, user friendly, and fully referenced. The system became operational in January 1996, and the first CME certificate was awarded to a participant shortly thereafter. CONCLUSIONS: Continuing medical education over the World Wide Web is an efficient means of delivering CME to the community at large; it allows participating physicians the latitude to obtain convenient CME credit at their leisure, in contrast to the regimented experience of formal CME conferences or symposiums. The interactive format of the CME cases allows the participant to submit immediate comments or criticism to case authors and receive instant feedback on their own performance, features unavailable in comparable educational software packages. The dynamic environment of the World Wide Web lends itself to the production and dissemination of such flexible forms of CME for the physician and will continue to expand in this capacity into the foreseeable future.

The Pittsburgh Reference Laboratory Alliance: a model for laboratory medicine in the 21st century.

The Pittsburgh Reference Library Alliance (RLA) represents a successful response by hospital laboratories to the new realities of medical economics and practice. By using informatics technology to integrate the laboratory resources of community hospitals and academic medical centers across western Pennsylvania, the RLA has created a large virtual laboratory that can compete for price with large national referral laboratories. More significantly, the combination of medical expertise, the ties to academic and community centers, and the regional medical database of the RLAs allows laboratory medicine to be practiced in a new proactive way. This should provide better and more cost-effective patient care. The success of the RLA is a model for regional cooperation in pathology and potentially in other medical specialties and demonstrates the importance of informatics in the future of medical practice.