Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Relationship between cognitive anxiety level and client variables at initial consultation for adults with hearing impairment.

UNLABELLED: The purpose of this study was to use the Cognitive Anxiety Scale (CAS) to investigate relationships between state-anxiety level (cognitive anxiety) and audiometric variables in adults with hearing impairment at their initial consultation. Thirty-five adults with hearing impairment who consulted an audiologist for the first time participated in this study. An interview to obtain information about cognitive anxiety was conducted prior to the audiological assessment. The results indicated that cognitive anxiety was significantly related to an ability to understand speech in noise. Further, cognitive anxiety and ability to understand speech in noise significantly contributed to the classification of hearing aid adopters and non-adopters. These results indicate that the measure of cognitive anxiety may have clinical applications in the future. LEARNING OUTCOMES: The reader will be able to: (1) discuss the relationship between anxiety and hearing impairment; (2) define cognitive anxiety; (3) state the relationship between cognitive anxiety and audiometric variables; (4) state the relationship between cognitive anxiety and the decision to adopt hearing aids; (5) identify signs of cognitive anxiety in adults with hearing impairment.

Development and field testing of a real-time PCR assay for cylindrospermopsin-producing cyanobacteria.

AIMS: To develop and test a real-time PCR assay to detect and quantify genes specific to Cylindrospermopsis sp. and cylindrospermopsin-producing cyanobacteria. METHOD AND RESULTS: A duplex real-time PCR assay was developed that targets a cylindrospermopsin-specific and Cylindrospermopsis raciborskii-specific DNA sequence. The C. raciborskii-specific sequence was based on the rpoC1 DNA-dependent RNA polymerase gene, whilst the cylindrospermopsin-specific sequence was selected by surveying an extensive number of potential cylindrospermopsin-producing cyanobacterial strains for genes implicated in toxin production, aoaA, aoaB and aoaC. In toxic strains, sequences of each of these three genes were always present; whilst in nontoxic strains the distribution of these sequences was patchy, resulting in what are likely to be natural deletion mutants. The real-time assay was optimized on a fixed and portable device, with results indicating that the reliable limit of detection for the assay was 100 copies per reaction or 1000 cells ml(-1) for both target sequences on both devices. In routine environmental samples enumerated by microscopy, the assay results were positive for all samples where C. raciborskii cells were observed at >1000 cells ml(-1) and negative in 15 samples where no C. raciborskii cells were observed. In field samples, the number of copies of the rpoC1 sequence more closely approximated the number of cells enumerated by microscopy, the number of copies of the pks sequence and detection of the toxin-specific sequence matched the results of toxin testing. CONCLUSIONS: The duplex real-time PCR assay was a sensitive and rapid method for detecting potential cylindrospermopsin-producing cyanobacteria in the laboratory or in the field. The observation of probable natural deletion mutants provides further evidence that the aoaA, aoaB and aoaC genes are involved in toxin production. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay provides a new monitoring capability for tracking cylindrospermopsin-producing cyanobacteria that are an emerging threat to water quality.

Molecular histology in the study of solid tumours.

Dominant oncogenes and tumour suppressor gene abnormalities are crucial events in human cancer. Many molecular techniques are used to identify these abnormalities, including single strand conformational polymorphism, the polymerase chain reaction, cloning, and sequencing, although the biological relevance of these changes is not always apparent. Immuno-histochemistry (ICH) or western blotting of abnormal gene products can provide information about their cellular localisation and expression in neoplastic versus normal cells, and can sometimes give a clue to their function. For example, ICH has shown how loss of the intercellular adhesion molecule E-cadherin, or abnormal localisation from the cell membrane to the cytoplasm, correlates with a diffuse tumour phenotype and a less favourable clinical outcome. Similarly, ICH of beta-catenin (a protein that binds E-cadherin and is essential for its function) has shown abnormal cellular localisation in the nucleus in a variety of human malignancies; in particular, colorectal carcinomas, where abnormal forms of the adenomatous polyposis coli gene product cause nuclear and cytoplasmic sequestration of beta-catenin. Such studies show how morphological assessment can sometimes provide insight into molecular function and dysfunction in human malignancy.

Predictors of advanced stage colorectal cancer diagnosis: results of a population-based study.

While colon cancer is a leading cause of morbidity and mortality among men and women, little is known about demographic variables associated with advanced stage diagnosis at diagnosis. We examined the relationship of age, gender, income, education, marital status, smoking status, urban versus rural residence, and proximal versus distal tumor location on stage at diagnosis. Data from Florida statewide cancer registry for the year 1994 with over 8,933 cases of colorectal cancer was analyzed. Using multivariate analysis, an odds ratio of being diagnosed with advanced stage disease was determined for each demographic variable. We found a significantly increased probability (P < .05) of diagnosis with advanced stage disease for distal lesions in middle-aged persons, smokers, and those with higher education or lower income status. If these findings are verified, they may suggest a group that warrants targeted screening intervention or programs over and above today's current colorectal screening recommendations.

Adrenocortical carcinoma metastatic to the orbit.

PURPOSE: To describe the clinical course and histopathologic features of a patient with adrenocortical carcinoma metastatic to the orbit. METHODS: Case report and literature review. RESULTS: A 24-year-old man first came to medical attention because of symptoms referable to a 4.47-kg, nonfunctioning carcinoma of the left adrenal cortex. Several metastases ensued, including a large tumor to the right superior lateral bony orbit with extension to the brain, temporalis fossa, and orbit proper. The tumor was resected with the use of a combined neurosurgical, ophthalmic, and craniofacial approach. The patient died of widespread metastatic disease 15 months after the orbital operation. CONCLUSIONS: Metastasis to the orbit from adrenocortical carcinoma is rare. Surgical resection is the treatment of choice, with adjunctive radiation therapy and chemotherapy in some cases. The prognosis is poor.

The association of hip strength and flexibility with the incidence of adductor muscle strains in professional ice hockey players.

This prospective study was conducted to determine whether hip muscle strength and flexibility play a role in the incidence of adductor and hip flexor strains in National Hockey League ice hockey team players. Hip flexion, abduction, and adduction strength were measured in 81 players before two consecutive seasons. Thirty-four players were cut, traded, or sent to the minor league before the beginning of the season. Injury and individual exposure data were recorded for the remaining 47 players. Eight players experienced 11 adductor muscle strains, and there were 4 hip flexor strains. Preseason hip adduction strength was 18% lower in the players who subsequently sustained an adductor muscle strain compared with that of uninjured players. Adduction strength was 95% of abduction strength in the uninjured players but only 78% of abduction strength in the injured players. Preseason hip adductor flexibility was not different between players who sustained adductor muscle strains and those who did not. These results indicate that preseason hip strength testing of professional ice hockey players can identify players at risk of developing adductor muscle strains. A player was 17 times more likely to sustain an adductor muscle strain if his adductor strength was less than 80% of his abductor strength.

Treatment of CMV retinitis with intravitral ganciclovir in the HAART era.

OBJECTIVE: To describe the course and outcome of cytomegalovirus (CMV) retinitis among AIDS patients treated with intravitreal ganciclovir and systemic highly active antiretroviral therapy (HAART). The secondary objective was to compare the course of CMV retinitis between patients receiving HAART and those not receiving this treatment. DESIGN: A retrospective cohort design consisting of 21 eyes from 16 patients with AIDS and CMV retinitis consecutively enrolled between January 1996 and August 1999. All patients received intravitreal ganciclovir therapy, and half of the patients began HAART as well. Duration of intravitreal therapy and ensuing disease quiescence, as well as CD4+ T cell counts at diagnosis and at cessation of ganciclovir, were calculated. Secondly, instantaneous hazards for outcomes such as CMV retinitis progression, ocular complications and mortality were compared. SETTING: Tertiary care centre in Ottawa, Ontario. RESULTS: Five of eight patients receiving HAART discontinued intravitreal ganciclovir after a mean treatment period of 428 days. During this period, their mean CD4+ count rose from 7.5 to 190microL. Subsequently, none of these patients experienced retinitis progression during follow-up periods lasting up to 820 days (mean of 617 days). Progression of CMV retinitis was 11.4 times more likely among those not receiving HAART (P=0.049). CONCLUSIONS: On initiating HAART, patients with CMV retinitis may enjoy significant recovery in CD4+ counts and sustained retinitis quiescence without specific anti-CMV therapy. Intravitreal ganciclovir injections seem well suited to offer effective CMV control during temporary periods of decreased CD4+ counts while awaiting HAART-mediated immune system reconstitution.

Pathology of late endothelial failure: late endothelial failure of penetrating keratoplasty: study with light and electron microscopy.

PURPOSE: Late endothelial failure of penetrating keratoplasty can be defined as gradual decompensation (increasing thickness with loss of clarity) of a previously clear graft without apparent cause. This study examined the possibility that a chronic subclinical rejection process may be occurring in grafts that fail from late endothelial failure. METHOD: Six patients fulfilling the diagnostic criteria for late endothelial failure who underwent repeated keratoplasty were studied. The clinical course and results of specular microscopy were reviewed. The failed corneal graft for each patient was examined by light and electron microscopy. RESULTS: Sequential specular microscopy demonstrated low initial postoperative endothelial cell density with continued decrease in density and increase in corneal thickness over the first 5 postoperative years. Electron microscopy revealed irregular-shaped cells of varying size with many abnormal features, lying on abnormal Descemet's membrane. Degenerating endothelial cells were commonly seen. There was no sign of acute or chronic inflammation. CONCLUSIONS: The pathologic findings are suggestive of an unstable and highly stressed endothelial cell population in late endothelial failure but are nonspecific. There was no evidence of acute or chronic rejection at the time of graft failure.

Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas.

PURPOSE: To describe the microcirculation architecture of metastatic choroidal and ciliary body melanoma. METHOD: Histologic sections of 35 metastases from 19 primary melanomas were stained to demonstrate microcirculation. RESULT: The appearance of microcirculatory networks in metastases is independent of the target organ but associated with the size of the metastatic deposit (estimated coefficient = 0.5959; SE = 0.3024; P = .0488). CONCLUSION: The microcirculatory patterns of primary uveal melanomas that are associated with metastatic behavior appear in foci of metastasis, regardless of the site of dissemination.

Cost-effectiveness in the diagnosis of sarcoidosis: the conjunctival biopsy.

PURPOSE: Sarcoidosis is a multi-system disease that often affects ocular structures. The definitive diagnosis of sarcoidosis requires tissue biopsy for confirmation. Conjunctival biopsy is a simple and relatively inexpensive diagnostic tool. This study was undertaken to determine the utility and cost of conjunctival biopsy for the diagnosis of sarcoidosis compared with other diagnostic biopsy sites. METHODS: A retrospective study was performed of all conjunctival biopsies taken for sarcoidosis at the Mayo Clinic Rochester between 1982 and 1995. All case histories were reviewed. Data regarding biopsy of tissues confirming sarcoidosis was collected. The costs of performing and evaluating all biopsy techniques were obtained from the estimating department. RESULTS: Forty-one cases of sarcoidosis were identified that had undergone conjunctival biopsies. Twenty-one patients had a positive conjunctival biopsy for sarcoidosis, and 20 patients had a negative conjunctival biopsy but a positive biopsy of another organ. In all positive biopsies, special stains for acid fast organisms and fungi were negative. CONCLUSIONS: Conjunctival biopsy is a simple, relatively inexpensive procedure that may be helpful in establishing the diagnosis of sarcoidosis with a negligible complication rate. Positive results are similar for conjunctival biopsy and mediastinoscopy. About 10 patients can be evaluated with conjunctival biopsy for the cost of one patient undergoing mediastinoscopy. Multiple levels of the tissue must be examined, as distribution of the granulomas may be random. Also, bilateral conjunctival specimens should be obtained to increase the positive yield.

Skeinoid fibers in mesectodermal leiomyoma of the ciliary body.

Unlike smooth muscle elsewhere in the body, the smooth muscle of the iris and ciliary body is derived from neuroectoderm (mesectoderm). Leiomyomas that arise from the ciliary body, and therefore are of mesectodermal origin, may resemble spindle cell neurogenic tumors by light microscopy. They show positive immunostaining for smooth muscle actin but negative staining for neural markers. Ultrastructurally, the cells have the features of smooth muscle cells. The authors report a typical case of mesectodermal leiomyoma in a 47-year-old woman in which skeinoid fibers, considered to be an ultrastructural marker of neurogenic spindle cell tumors, were frequent together with other ultrastructural features often seen in neuroglial cell tumors. The findings indicate that mesectodermal leiomyoma is unique in its histogenesis as well as in its morphology.

Histopathologic study of eyes after iodine I 125 episcleral plaque irradiation for uveal melanoma.

OBJECTIVES: To describe the histopathologic findings attributable to irradiation in eyes with uveal malignant melanoma treated with iodine I 125 brachytherapy and to compare these findings with those reviewed in a previous study that compared histopathologic findings in eyes enucleated after proton beam teletherapy with those seen in eyes in a nonirradiated control group. METHODS: The slides from 22 eyes with uveal melanoma that had undergone enucleation after the administration of 125I brachytherapy were studied. The histopathologic features of the tumor and the retina were graded. Results were compared with findings from a previously reported group of 47 proton beam-treated eyes and its control group. RESULTS: Patient age, time between irradiation and enucleation, and ciliary body involvement were similar for the 125I brachytherapy-treated group and the proton beam-treated group and its control group. This allows comparison of the histopathologic findings. Comparing the 125I brachytherapy- and proton beam-treated groups, most histopathologic features were similar with nominally statistically significant differences only for cell type, number of mitotic figures, and fibrous metaplasia of the retinal pigment epithelium adjacent to the tumor. CONCLUSIONS: Irradiation of uveal melanoma induces changes in the tumor and in the surrounding retina. Brachytherapy and charged particle therapy are the 2 principal methods of irradiation. This study demonstrates that similar changes are produced by 125I plaque irradiation and proton beam irradiation.

Vortex keratopathy in a patient with multiple myeloma.

PURPOSE: We report a 52-year-old woman with vortex keratopathy (cornea verticillata) of unknown cause in whom multiple myeloma was found 18 months later. METHODS: Surgical biopsy of conjunctival crystalline deposits, which were stained immunohistologically and analyzed ultrastructurally, as well as hematologic workup for multiple myeloma, were performed. RESULTS: Light microscopy of conjunctival deposits revealed plasmacytoid infiltrates in the conjunctiva, which stained monoclonally for immunoglobulin G (IgG)-kappa light chains. Transmission electron microscopy showed intracellular hexagonal crystalline structures and extracellular microfibrils. Hematologic tests confirmed the diagnosis of multiple myeloma. CONCLUSION: Multiple myeloma is one of the many causes of vortex keratopathy.

Intravitreal invasion of malignant cells from choroidal melanoma after brachytherapy.

We report intravitreal invasion by melanoma cells from a choroidal melanoma after brachytherapy. A malignant melanoma of the choroid with collar-button configuration was treated with iodine 125 brachytherapy. Years later, the collar button developed a dark-chocolate color and began shedding pigmented debris into the vitreous. Coalescence of this debris into spheroidal aggregates suggested the presence of malignant cells; the eye was enucleated. Histologic sections demonstrated a choroidal melanoma with intraretinal and intravitreal invasion by melanoma. Clinical evidence of intraretinal invasion by melanoma cells along with pigmented debris within the vitreous cavity, especially when clustered in spheroidal aggregates, suggests the presence of intravitreal invasion by malignant cells. In this case, intravitreal invasion was verified histologically.

Familial subepithelial corneal amyloidosis--a lactoferrin-related amyloidosis.

PURPOSE: To isolate the protein that collects in increased amounts beneath the corneal epithelium in familial subepithelial corneal amyloidosis (FSCA), also known as gelatinous droplike corneal dystrophy, and to identify it by N-terminal amino acid sequencing. METHODS: Peptides resulting from pepsin digestion of a unique protein isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from frozen tissue from two corneas with FSCA were purified by high-pressure liquid chromatography followed by protein sequence analysis. The protein was identified by amino acid sequencing, Western blotting, and immunohistochemistry. RESULTS: A protein was identified in two corneas with FSCA that was not present in normal corneas or in corneas with other disorders. The amino acid sequences of two peptides derived from this protein were identical to portions of lactoferrin. The unique protein reacted with rabbit antihuman lactoferrin after Western blotting. The presence of lactoferrin in the amyloid within affected corneas was confirmed using the immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections and lactoferrin antiserum. CONCLUSIONS: Corneal tissue with FSCA contains lactoferrin, and this is the first form of amyloidosis found to be associated with this protein. Because lactoferrin is a product of lacrimal glands, the corneal lactoferrin may be derived from the tears. Because the gene for lactoferrin is on chromosome 3 (3q21-q23), this locus is a potential site for the FSCA gene.

Succinate dehydrogenase activity within synaptic and extrasynaptic compartments of functionally-overloaded rat skeletal muscle fibers.

Activity of the mitochondrial enzyme succinate dehydrogenase (SDH) was assessed using quantitative microphotometric techniques within postsynaptic, subsarcolemmal and intermyofibrillar compartments of overloaded soleus muscle fibers. Six weeks of overload, induced via synergist tenotomy, significantly increased soleus muscle mass (23%) and mean fiber cross-sectional area (17%). Despite these increases in cell size, SDH activity within all three intracellular compartments of overloaded muscle fibers was not different from levels in corresponding regions of control fibers. Thus, we show for the first time that activity-related increases in muscle cell volume, and specifically motor endplate area, appear to be coordinated with increased levels of oxidative enzymes within distinct subcellular compartments, including the postsynaptic sarcoplasm.