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Biomedical subjects

R J Higgins

Publications and source records attributed to R J Higgins.

At least 19 recordsLinked to original sources
PubMed2006

Canine intraneural perineurioma.

A 6-year-old castrated German Shepherd Dog was presented with a 6-month history of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots after later amputation revealed distended hypercellular fascicles. This distension was due to widely separated axons surrounded by concentric lamellations formed by neoplastic perineurial cells and their processes. These pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma. The perineurioma cell processes were immunonegative for S-100 (alpha and beta chains) and collagen IV, but were immunoreactive for laminin. The central axons were also immunoreactive for NF-200 and S-100. The proliferative index of the perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%. Ultrastructurally, the widely separated, interdigitating perineurioma cell processes were connected by desmosomal-like junctional complexes to form continuous circles. Their processes were covered by a discontinuous basal lamina. Each centrally placed axon was normally, thinly, or completely unmyelinated and was surrounded by a normal Schwann cell. These morphologic and immunologic features distinguish this lesion from hypertrophic neuropathy and were consistent with intraneural perineurioma.

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PubMed2005

Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy.

Central nervous system (CNS) tissues from 192 cats with neurological signs were examined histologically, and tissues from 173 of them were later examined immunohistochemically as part of a survey to determine the prevalence of feline spongiform encephalopathy (FSE). One of the cats was from Norway and the others were from Great Britain. The most commonly recorded clinical signs were ataxia, behavioural changes and epilepsy, but none of the cats had histopathological evidence of FSE. The most common organic CNS lesions were non-suppurative encephalomyelitis in 28 per cent, neoplasia in 15 per cent and a heterogeneous group of degenerative encephalopathies in 9 per cent of the cats. A range of minor histological lesions of uncertain significance was also observed. No histological lesions were observed in the tissues of 63 (33 per cent) of the cats. Disease-specific prion protein (PrP(Sc)) was observed in only one of the 173 cats examined by immunohistochemistry.

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PubMed2004

Primary intra-axial leiomyosarcoma with obstructive hydrocephalus in a young dog.

A female Chihuahua dog aged 2 months had a 3-week history of progressive neurological signs (abnormal behaviour, disorientation, left-sided circling, and incessant whimpering). Necropsy revealed a primary leiomyosarcoma in the midline of the posterior thalamus with secondary obstructive hydrocephalus of the lateral ventricles. Grossly, an infiltrative, grey-white tumour had partly invaded the third ventricle. Histologically, the tumour formed hypercellular, interlacing bundles of neoplastic spindle cells with blunt-ended nuclei. Neoplastic cells were strongly immunoreactive for vimentin and both muscle-specific and alpha-smooth muscle actin; MIB-1 immunoreactivity indicated a proliferative index of up to 5%. Leiomyosarcoma should be included in the differential diagnosis for primary brain tumours and hydrocephalus in young dogs.

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PubMed2004

A peripheral primitive neuroectodermal tumor with generalized bone metastases in a puppy.

A peripheral primitive neuroectodermal tumor (pPNET), most consistent with a human Ewing's sarcoma, is described in a 5-month-old male Australian Shepherd puppy. The first tumor site detected was in the left frontal bone of the skull with apparent subsequent rapid metastases to multiple sites in the axial and appendicular skeleton and bone marrow, kidneys, and perihyphophyseal meninges. Radiographically, all bone lesions were lytic and there was also a humeral bone fracture. Histologically, the tumor was diagnosed as a small round blue cell tumor. At this stage, the differential diagnosis included a lymphoma, rhabdomyosarcoma, and a PNET of the peripheral nervous system. However, the cells had positive expression of triple neurofilament antigens as detected immunocytochemically. The cells were negative for a broad panel of canine-specific leucocyte cell marker antigens for desmin, smooth muscle actin, synaptophysin, and CD99. Ultrastructurally, the cells contained occasional dense core neurosecretory granules and intermediate filaments with intercellular desmosomal-like junctions and abundant glycogen clusters. Based on the age of the dog, the clinical history, the distribution of gross lesions, histologic characteristics of a small round blue cell tumor, and immunocytochemical and ultrastructural evidence of neuroectodermal differentiation, a diagnosis of a pPNET similar to a human Ewing's sarcoma was made.

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PubMed2003

Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs.

Although glioblastoma multiforme (GBM), a World Health Organization grade IV astrocytoma, is the most common primary brain tumor in humans, in dogs GBM is relatively rare, accounting for only about 5% of all astrocytomas. This study presents combined clinical, neuroimaging, and neuropathologic findings in five dogs with GBM. The five dogs, aged from 5 to 12 years, were presented with progressive neurologic deficits that subsequent clinical neurologic examination and neuroimaging studies by magnetic resonance imaging (MRI), localized to space occupying lesions in the brain. MRI features of the tumors included consistent peritumoral edema (n = 5), sharp borders (n = 4), ring enhancement (n = 3), heterogenous T2-weighted signal intensity (n = 3), iso- to hypointense T1-weighted images (n = 5), necrosis (n = 5), and cyst formation (n = 2). Two tumors were diagnosed clinically using a computed tomography-guided stereotactic biopsy procedure. At necropsy all the tumors resulted in, on transverse sections, a prominent midline shift and had a variegated appearance due to intratumoral necrosis and hemorrhage. Histologically, they had serpentine necrosis with glial cell pseudopalisading and microvascular proliferation, features which distinguish human GBM from grade III astrocytomas. Immunoreactivity of tumor cells for glial fibrillary acidic protein was strongly positive in all cases, whereas 60% and 40% of the tumors also expressed epidermal growth factor receptor and vascular endothelial growth factor, respectively. These canine GBMs shared many diagnostic neuroimaging, gross, microcopic, and immunoreactivity features similar to those of human GBMs.

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PubMed2002

Porcine dermatitis and nephropathy syndrome. clinical and pathological features of cases in the United Kingdom (1993-1998).

This paper documents the salient clinical and pathological features of porcine dermatitis and nephropathy syndrome (PDNS) in 96 pigs submitted from 55 units in the UK from 1993 to 1998. This series of cases pre-dated the emergence of post-weaning multisystemic wasting syndrome (PMWS) in the UK. The morbidity during outbreaks was 1% or less. Affected pigs ranged from 14 to 70 kg in weight and most died after a short clinical illness. Fifty-five pigs had multifocal or coalescing erythematous skin lesions, some progressing to dermal necrosis. Biochemistry showed raised serum urea, creatinine and gamma globulin levels accompanied by proteinuria. All cases showed bilateral renal enlargement with petechiae throughout the cortices. Microscopically these renal lesions ranged in chronology from acute necrotizing glomerulitis and vasculitis with multiple hyaline casts in renal tubules to chronic glomerular sclerosis with interstitial inflammation and fibrosis. Haemorrhagic dermatitis when present was associated with necrotizing vasculitis in the dermal vessels. Vasculitis was sometimes detected in other tissues including subcutis, lymph nodes, spleen, liver, joint synovial membrane, gastric and intestinal submucosa or serosa and meninges but its frequency and distribution varied considerably in individual pigs. Immunostaining showed deposits of IgG and IgM in damaged glomeruli, renal casts and skin lesions. The aetiology and pathogenesis of the condition remain unknown but the histopathological and immunological findings suggest a systemic immune-complex disorder resulting in vasculitis with particular predilection for kidney and skin.

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PubMed2001

Primary canine and feline nervous system tumors: intraoperative diagnosis using the smear technique.

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.

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PubMed2001

Granular cell tumor of the canine central nervous system: two cases.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.

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PubMed2000

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.

In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).

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PubMed2000

Clinical and pathologic features of oligodendrogliomas in two cats.

Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.

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PubMed1999

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.

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