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.

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.

Sebaceous carcinoma of the eyelid. Errors in clinical and pathologic diagnosis.

Sebaceous carcinoma of the eyelid is commonly misdiagnosed because it simulates other entities both clinically and pathologically. In a review of all pathologic material removed from the eyelids of patients at the Mayo Clinic between 1905 and 1981, 43 sebaceous carcinomas were discovered. The tumors manifested most frequently on the upper eyelid; the onset of symptoms occurred in 31 women and 12 men at a mean age of 61.5 years (range, 28-82 years). Of the 43 patients, 11 had an associated second malignant tumor or exposure to irradiation. The microscopic diagnosis was based on finding a proliferation of basophilic neoplastic cells with foamy cytoplasm and a positive fat stain. Intraepithelial neoplasia in the form of pagetoid change or carcinoma in situ was found in more than 80% of cases. Histologically, the tumor tended to be moderately differentiated. A high degree of infiltration was frequently observed cases with metastases. When intraepithelial neoplasia is observed microscopically, we recommend a fat stain on a frozen section and a full-thickness eyelid biopsy to exclude sebaceous carcinoma.

Immunoreactivity for estrogen receptor protein in sweat gland tumors.

The histologic and immunophenotypic similarities between sweat gland carcinoma and breast cancer are well known. Indeed, these likenesses often preclude the diagnostic separation of primary cutaneous glandular neoplasms from metastatic mammary carcinomas, based on light microscopic and immunohistochemical features alone. To assess whether the presence of estrogen receptor protein (ERP) in breast carcinoma might serve as a diagnostic marker in this context, we analyzed 33 eccrine carcinomas, 24 sebaceous carcinomas, 15 intraepidermal apocrine carcinomas (extramammary Paget's disease), and 42 benign sweat gland tumors for ERP content. The monoclonal anti-ERP H222 was used with a modified avidin-biotin-peroxidase complex (ABC) method and paraffin sections. For comparison, eight cutaneous metastases of mammary carcinomas were similarly studied. ERP was identified in six of eight secondary neoplasms. However, this steroid-binding protein also was detected in 10 of 33 eccrine carcinomas. In three of 10 eccrine hidradenomas, each of two examples of hidradenoma papilliferum, and two of three chondroid syringomas, ERP-reactivity was noted as well. The remaining eccrine, apocrine, and sebaceous neoplasms were nonreactive. Among immunoreactive eccrine neoplasms, eight of 10 carcinomas occurred in males, whereas most ERP-positive benign eccrine tumors arose in females. The potential expression of ERP by sudoriferous malignancies reinforces the biologic similarities between mammary and cutaneous adnexal neoplasms. Moreover, ERP reactivity in the latter lesions underscores the inability of immunohistochemistry to distinguish primary and secondary glandular tumors of the skin with certainty.

Calcification in retinoblastoma.

Review of 40 cases of retinoblastoma revealed that histologic evidence of calcification was noted in 38 of the 40 tumors, whereas only three of 16 roentgenograms were positive for calcium. Calcificaton detected by roentgenograms and histopathologic examination correlated poorly with quantitative determination for tumor calcium. Compared to control eyes, however, eyes with retinoblastoma contain large amounts of calcium (1.2 vs. 218 mug/ml. ash). This calcification, though frequently not observed in standard roentgenograms, should be detected by the newer diagnostic modalities such as hypocycloidal polytomography, computerized transaxial tomography, ultrasonography, and radionuclide scintigraphy with technetium diphosphonate, a bone-scanning agent.

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.

Painful ophthalmoplegia (Tolosa-Hunt variant): autopsy findings in a patient with necrotizing intracavernous carotid vasculitis and inflammatory disease of the orbit.

A 79-year-old man with unremitting painful ophthalmoplegia had a necrotizing inflammatory process that involved the intracranial and intracavernous portions of the right internal carotid artery. The condition ultimately resulted in rupture of the carotid vessel and death. At autopsy, thrombophlebitis of the sphenopalatine sinus was also noted. To our knowledge, this is the second reported autopsy study of painful ophthalmoplegia and chronic nongranulomatous inflammation that involved the carotid siphon and the cavernous sinus.

Primary intraorbital meningioma with intraocular extension.

Intraocular invasion of a meningioma primary in the sheath of the intraorbital portion of the optic nerve was noted in a 54-year-old woman with a 16-year history of visual loss. Seventeen additional cases of intraglobal extension of intraorbital meningioma were found in the literature. The clinical features and histopathologic findings of the total cases are compared and reviewed. We suggest that the mode of penetration is along the course of the posterior ciliary vessels as they penetrate the sclera.

Clinicopathologic studies of primary cerebral amyloid angiopathy.

Primary cerebrovascular amyloidosis resulting in significant cerebral parenchymal damage was encountered in 23 autopsied cases at the Mayo Clinic over the past 10 years. Patients were 60 to 97 years old and both sexes were equally represented. Large- and medium-sized leptomeningeal and cortical arteries showed the characteristic pattern of medial and intimal involvement, with luminal stenosis. The walls of smaller arteries were often diffusely infiltrated, with fibrinoid degeneration and miliary aneurysm formation. The amyloid nature of the infiltrate was confirmed by electron microscopic examination in all cases. All cases showed varying numbers of perivascular or independent senile plaques in the cerebral cortex. Alzheimer's neurofibrillary tangles were absent or were limited to the hippocampal region in all but two cases. Multiple, small cortical infarcts and hemorrhages were regularly present. Larger hemorrhage was present in nine cases. Of nine patients with terminal massive cerebral hemorrhage, only two were hypertensive. Six patients had had progressive dementia; four had had single episodes of vascular events and seven, multiple episodes; and four had had both dementia and vascular episodes. Primary cerebral amyloid angiopathy should be regarded as an important cause of mental deterioration and fatal cerebrovascular accidents in the elderly.

Osteoma: an unusual cause of amaurosis fugax.

A 16-year-old white boy presented with a history of amaurosis fugax associated with an afferent pupillary defect, proptosis, discomfort of the left eye. Tomograms of the skull and of the orbit revealed a lobulated 4-cm ivory osteoma arising from the left ethmoid sinus and extending into the maxillary sinus and left orbit. After surgical extirpation, visual acuity returned to normal and the papilledema resolved after 4 months. This patient is 1 of 37 patients with osteoma of the paranasal sinuses or of the orbit (or of both) who underwent surgical treatment at the Mayo Clinic between the years 1948 and 1977. Twelve of these patients had orbital involvement, and only these patients had ocular signs and symptoms.

Arteriovenous malformation affecting the transverse dural venous sinus--an acquired lesion.

Dural arteriovenous malformations of the transverse sinus are relatively well localized to the occipitomastoid regions and occur predominantly in women who are more than 40 years of age. The signs and symptoms, except for pulsatile tinnitus, vary and apparently depend on the presence of impaired venous drainage, which may produce increased intracranial pressure, papilledema, and transient or persistent neurologic deficits. Eight of the 14 patients described had occlusion of one or both transverse or sigmoid sinuses. Two patients had angiographic demonstration of sigmoid or transverse sinus occlusion (one 1 year and the other 4 years) before the development of an arteriovenous malformation in the appropriate sinus. Dural sinus occlusion may precede the development of a dural arteriovenous malformation, and the pathogenesis may be partial recanalization of a thrombus.

Skip lesions in temporal arteritis.

Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.

The pituitary gland in the Laurence-Moon syndrome.

The apparent hypogonadism in patients with the Laurence-Moon syndrome has been variably attributed to unresponsiveness of target organs to gonadal hormones, primary end-organ failure, hypothalamic dysfunction, or pituitary failure. We report the first immunocytologic study of the pituitary gland in this rare disorder. No morphologic abnormalities were noted. The numbers and immunoreactivities of adenohypophyseal cell types were normal. No microscopic abnormalities were evident in the hypothalamus and target organs. The results of our study are consistent with recent biochemical data that suggest that pituitary function is normal in patients with this syndrome.

Are brief pulse and sine wave ECT equally efficient?

The literature reflects that brief pulse electroconvulsive therapy (ECT) uses less energy to elicit seizures and produces less cognitive disturbance than does sine wave ECT. However, the relative effectiveness and efficiency of the two waveforms have not been firmly established. In an effort to clarify these issues, the authors retrospectively compared a diagnostically heterogeneous group of 197 patients who received sine wave ECT with a similar group of 144 patients who received brief pulse ECT. The average number of ECT treatments administered to each group was essentially the same. Among a more homogeneous group of patients with affective disorders treated with either bilateral or mixed electrode placements, the number of treatments required with each waveform did not differ significantly.

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.

Double phakomatosis.

In the phakomatoses--von Recklinghausen's disease, the Sturge-Weber syndrome, tuberous sclerosis, and von Hippel-Lindau disease--pathologic changes in the eye are often evident. Most cases are described as a single entity. The following is a case report of concomitant Sturge-Weber syndrome and von Recklinghausen's disease in which both conditions involved the eye.

Mayo Clinic experience with conjunctival melanomas.

One hundred twenty-six surgically excised pigmented lesions of the conjunctiva were evaluated and correlated with clinical data and follow-up information. Of these, 42 were classified as conjunctival melanomas, with 18 arising apparently de novo, 15 from acquired melanosis, and nine from nevi. The six tumor deaths occurred only in patients with melanomas arising de novo or from acquired melanosis, Patients with tumor deaths usually demonstrated local recurrences long before metastases occurred. Moreover, several patients had local recurrences treated repeatedly for years without metastatic spread. Recent clinical findings relating to skin melanomas were applied and evaluated.

Aspergillus terreus endophthalmitis in a patient with chronic lymphocytic leukemia.

A 65-year-old woman with a 7-year history of chronic lymphocytic leukemia presented with acute visual loss, pain, and redness in her right eye. Results of stains and cultures of anterior chamber fluid were negative. Neurologic problems, bronchopulmonary pneumonia, recurrent skin lesions, and a low-grade fever developed. Progressive respiratory distress ensued, and the patient died 1 month after presentation. Cultures from antemortem sputum and skin samples were positive for Aspergillus terreus. Postmortem histologic results showed extensive A terreus invasion of the posterior vitreous, retina, choroid, and anterior optic nerve. This organism was also found in histologic sections from the right adrenal gland, left kidney, thyroid, urinary bladder, right lung, skin, esophagus, sputum, vessels of the myocardium, and brain. To our knowledge, A terreus endophthalmitis has not been reported previously.

Endothelial changes in rabbit corneas. Observation by specular microscopy during storage in McCarey-Kaufman (M-K) medium.

Corneal banks are beginning to screen donor tissue with a specular microscope to detect abnormal endothelium. To determine the appearance of normal corneal endothelium under storage conditions, the endothelium of healthy rabbit corneas was examined with a modified specular microscope while being stored in McCarey-Kaufman (M-K) medium at 4 degrees C. Black areas within endothelial cells and decreased clarity of the endothelial cell borders were observed during storage and were found to be reversible on warming of the M-K medium.