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Biomedical subjects

J D Slater

Publications and source records attributed to J D Slater.

At least 55 records · Page 3Linked to original sources
PubMed1997

Detection and distribution of equine herpesvirus 2 DNA in the central and peripheral nervous systems of ponies.

The distribution of equine herpesvirus 2 (EHV-2) DNA within neurological and lymphoid tissues from 12 EHV-2 seropositive Welsh mountain ponies was determined by PCR. The lymphoid sites sampled in this study were almost universally PCR positive, thus confirming the existing virus co-cultivation data which suggest that the lymph nodes draining the respiratory tract are the main reservoirs of EHV-2 DNA. In addition, EHV-2 DNA was also detected, albeit with lower frequency, within both the peripheral and central nervous systems (PNS and CNS) of these animals. Of the CNS sites sampled 11% were PCR-positive and in the PNS the trigeminal ganglion proved PCR-positive in 50% of the animals tested. Since the nasal epithelium is innervated by the maxillary division of the trigeminal nerve, these observations suggest that the trigeminal ganglion may represent a biologically important site for EHV-2 latency.

Animals↗
PubMed1997

Transmission of equine herpesvirus 2 to the mouse: characterization of a new laboratory infection model.

Intranasal inoculation of BALB/c mice with a recent clinical isolate of equine herpesvirus 2 (EHV-2 strain MR) produced a productive infection characterized by clinical signs, including weight-loss and conjunctivitis, but no mortality. Infectious virus was isolated from the lung, trachea and nasal turbinates with the highest titres present in lung tissue; EHV-2 neutralizing antibody was detected in the serum on day 21 post-inoculation. No infectious virus was detected in neural tissue, blood or lymphoid tissues. An EHV-2-specific nested PCR confirmed the presence of EHV-2 DNA in the respiratory tissues. In addition, EHV-2 DNA was detected in the trigeminal ganglia and olfactory bulbs from the first day after inoculation and these tissues remained positive for EHV-2 DNA for at least 30 days, by which time EHV-2 DNA had been cleared from all other tissues.

Animals↗
PubMed1996

Phase I/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results.

PURPOSE: Age-related macular degeneration is the prevalent etiology of subfoveal choroidal neovascularization (CNV). The only effective treatment is laser photocoagulation, which is associated with decreased visual acuity following treatment in most patients. This study assessed both the response of subfoveal CNV to proton beam irradiation and treatment-related morbidity. We evaluated preliminary results in patients treated with an initial dose of 8 Cobalt Gray Equivalents (CGE) using a relative biological effectiveness (RBE) of 1.1. METHODS AND MATERIALS: Twenty-one patients with subfoveal CNV received proton irradiation to the central macula with a single fraction of 8 CGE; 19 were eligible for evaluation. Treatment-related morbidity was based on Radiation Therapy Oncology Group (RTOG) criteria; response was evaluated by Macular Photocoagulation Study (MPS) guidelines. Fluorescein angiography was performed; visual acuity, contrast sensitivity, and reading speed were measured at study entry and at 3-month intervals after treatment. Follow-up ranged from 6 to 15 months. RESULTS: No measurable treatment-related morbidity was seen during or after treatment. Of 19 patients evaluated at 6 months, fluorescein angiography demonstrated treatment response in 10 (53%); 14 (74%) patients had improved or stable visual acuity. With a mean follow-up of 11.6 months, 11 (58%) patients have demonstrated improved or stable visual acuity. CONCLUSION: A macular dose of 8 CGE yielded no measurable treatment morbidity in patients studied. Fluorescein angiography demonstrated that regressed or stabilized lesions were associated with improved visual acuity as compared with MPS results. In the next phase, a dose of 14 CGE in a single fraction will be used to further define the optimal dose fractionation schedule.

Aged↗
PubMed1996

Computed tomography slice-by-slice target-volume delineation for stereotactic proton irradiation of large intracranial arteriovenous malformations: an iterative approach using angiography, computed tomography, and magnetic resonance imaging.

PURPOSE: Target-volume delineation for stereotactic irradiation is problematic for large and irregularly shaped arteriovenous malformations (AVMs). The purpose of this report is to quantify modifications in the target volume that result from iterative treatment planning that incorporates multimodality imaging data. METHODS AND MATERIALS: Stereotactic neuroimaging procedures were performed for 20 consecutive patients with AVM volumes > 10 cm3. Angiographically defined extrema were transformed into computed tomography (CT) space. The resulting target contours were then modified by a multidisciplinary treatment planning team after iterative review of angiographic, CT, and magnetic resonance imaging (MRI) data. Volumes of interest and dose-volume histograms for proton irradiation were calculated before and after iterative target delineation. RESULTS: Initial (angiographically defined) target volumes ranged from 15.3 to 96.1 cm3 (mean, 43.6 cm3). Final (iteratively defined) target volumes ranged from 10.7 to 114.0 cm3 (mean, 38.4 cm3). The volume of presumed normal tissue excluded by iterative planning ranged from 2.6 to 47.0 cm3 (mean, 15.5 cm3). Initially untargeted AVM, most commonly obscured by embolization material, was identified in all cases (range, 0.3 to 57.8 cm3; mean, 10.3 cm3). Corresponding dose-volume histograms demonstrated marked differences regarding lesion coverage and sparing of normal tissue structures. CONCLUSIONS: Iterative target-volume delineation resulted in significant modifications from initial, angiographically defined target volumes. Substantial amounts of apparently normal tissue were excluded from the final target, and additional abnormal vascular structures were identified for incorporation. We conclude that an iterative multimodality approach to target-volume delineation may improve the overall results for stereotactic irradiation of large and complex AVMs.

Humans↗
PubMed1995

Concurrent radiation therapy and chemotherapy in the treatment of primary squamous cell carcinoma of the vulva.

BACKGROUND: Interest in combined modality treatment and in quality of life issues may affect the choice of radical vulvectomy as the treatment of choice in many vulvar carcinomas. To evaluate the potential role of combined radiation and chemotherapy with or without local excision as primary treatment for squamous cell carcinoma of the vulva, the outccomes of 19 patients with this disease treated with combination therapy were reviewed. METHODS: Nineteen patients were treated between September 1987 and October 1992. Fifteen patients had American Joint Committee on Cancer Stage III disease; 4 had Stage II. All had clinically negative inguinal lymph nodes with the exception of two patients who had positive ipsilateral inguinal nodes that were removed before treatment. The patients received 45-50 Gy to the pelvis and inguinal nodes with concurrent chemotherapy that consisted of 5-fluorouracil given as a 96-hour continuous infusion (1000 mg/m2/d) during weeks 1 and 5 of radiation. A single dose of mitomycin-C (10 mg/m2) during the first day of chemotherapy has been used since November 1991. Ten patients were boosted with implants or electrons and 6 others underwent local excision. RESULTS: The median follow-up was 34 months. Responses were determined clinically 1 month after completion of the radiation and chemotherapy. Clinically, complete responses were obtained in 10 patients (53%), partial responses in 7 (37%), and no response in 1; 1 patient progressed during treatment. The combined modality therapy (radiation/chemotherapy/with or without wide local excision) resulted in a local control rate of 74% (14/19). All five treatment failures occurred within 6 months of treatment. Four of these patients were rendered disease free by radical vulvectomy and/or exenteration, for an overall local control rate of 95% (18/19). CONCLUSION: Concurrent radiation therapy and chemotherapy with local excision performed as needed, appears to be a reasonable alternative to radical vulvectomy in patients with primary squamous cell carcinoma of the vulva. Radical surgery remains a viable option for patients in whom primary therapy has failed.

Adult↗
PubMed1995

Proton therapy for cranial base tumors.

Proton irradiation and other charged-particle modalities have demonstrated effectiveness in controlling cranial base tumors and other lesions. The combination of capabilities available with heavy charged particles makes for a desirable therapeutic option that offers the opportunity for tumor ablation while preserving normal tissue function, with obvious implications for quality of life.

Chondrosarcoma↗
PubMed1995

The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons.

Neural tissues from specific pathogen-free ponies that had been experimentally infected with equine herpesvirus 1 (EHV-1) were analysed by in situ hybridization. Digoxigenin-labelled EHV-1 BamHI fragments spanning almost the entire EHV-1 genome were hybridized to RNA in tissue sections from latently infected trigeminal ganglia. The BamHI E fragment detected EHV-1 RNA antisense to gene 63 (HSV-1 homologue ICP0) in a small number of neurons. Sixteen other BamHI fragments gave negative results in 20 sections tested with each fragment. Latency associated transcripts (LATs) were localized to the neuronal nuclei. EHV-1 nucleotide sequence data in the region reveals the presence of a putative EHV-1 LAT promoter that shares a similar motifs with the HSV-1 LAT promoter, including the LAT promoter-binding factor, and may have a role in EHV-1 LAT expression.

Amino Acid Sequence↗
PubMed1995

Induction of pseudoseizures with intravenous saline placebo.

For a 2-year period, all patients admitted to the inpatient adult EEG videotelemetry unit of the University of Miami School of Medicine underwent attempted event induction with intravenous normal saline placebo. Of 175 patients monitored during that period, 101 underwent attempted placebo saline induction, whereas 58 patients were either in the pediatric age group, were undergoing a repeat hospitalization (i.e., depth electrode monitoring), or refused induction. The final diagnosis in each patient was established after review of the history; physical, interictal, and ictal EEG findings; brain imaging studies; interictal and postictal brain single photon emission computed tomography (SPECT) and serum prolactin levels; psychiatric and psychological evaluations; and detailed neuropsychological testing. Final diagnoses were separated into epilepsy alone, pseudoseizures, epilepsy and pseudoseizures, and other (neither epilepsy nor pseudoseizures). No patient with an eventual diagnosis of epilepsy alone was inducible. Forty-one patients with a diagnosis of epilepsy were not inducible. Of 32 patients with an eventual diagnosis of pseudoseizures, 29 were inducible. One of these 29 was also diagnosed with epilepsy. Three patients with an eventual diagnosis of pseudoseizures were not inducible; 90.6% of patients with an eventual diagnosis of pseudoseizures were inducible, i.e., had events identical to those reported by history, after injection of saline placebo. Placebo saline injection is a safe and effective means of distinguishing epilepsy from pseudoseizures.

Adult↗
PubMed1995

Echocardiographic measurements of cardiac dimensions in normal ponies and horses.

Echocardiographic examinations were performed on 41 clinically normal small ponies, large ponies and horses. Using standardised two-dimensional (2-D) echocardiographic images to guide M-mode studies, the interventricular septal thickness, left ventricular internal dimension and left ventricular wall in systole and diastole, and aortic diameter in diastole were measured. Normal values for these echocardiographic dimensions were obtained across a wide range of bodyweights. Although there was a trend for echocardiographic dimensions to increase with bodyweight across the whole range of animals examined, little or no linear correlation was found between dimensions and bodyweight within the small pony, large pony and horse groups.

Aging↗
PubMed1994

Neural network analysis of the P300 event-related potential in multiple sclerosis.

Neural network analysis is sensitive to subtle changes in patterns of data. We hypothesized that a disease process which can cause impairment of cortical function such as multiple sclerosis (MS) would affect the P300 cognitive evoked potential (P300) in a manner detectable by a feedforward backpropagation neural network. Such a network was trained using a learning data set consisting of 101 P300 wave forms (from 26 MS patients and 26 normal controls). The network was then used to classify a randomly selected test data set of 20 studies (2 studies each of 5 MS patients and 5 controls) to which it had not been previously exposed, with an average accuracy (MS = abnormal, control = normal) of 81% for a single midline electrode, increasing to 90% using 3 midline electrodes in a jury system. Neural network analysis can be of help in distinguishing normal (control) P300 from abnormal (MS) P300.

Acoustic Stimulation↗
PubMed1994

Neural network approach in multichannel auditory event-related potential analysis.

Even though there are presently no clearly defined criteria for the assessment of P300 event-related potential (ERP) abnormality, it is strongly indicated through statistical analysis that such criteria exist for classifying control subjects and patients with diseases resulting in neuropsychological impairment such as multiple sclerosis (MS). We have demonstrated the feasibility of artificial neural network (ANN) methods in classifying ERP waveforms measured at a single channel (Cz) from control subjects and MS patients. In this paper, we report the results of multichannel ERP analysis and a modified network analysis methodology to enhance automation of the classification rule extraction process. The proposed methodology significantly reduces the work of statistical analysis. It also helps to standardize the criteria of P300 ERP assessment and facilitate the computer-aided analysis on neuropsychological functions.

Algorithms↗
PubMed1994

The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse.

Four specific pathogen-free ponies were infected intranasally with equine herpesvirus 1 (EHV-1) and two were similarly infected with an EHV-1 thymidine kinase deletion mutant. The primary infections were characterized by a transient fever accompanied by virus shedding into nasal mucus and viraemia. No virus was detected in clinical specimens after 15 days post-infection. Two months later a reactivation stimulus was administered to all six ponies and only the four that had been previously inoculated with wild-type EHV-1 shed virus into nasal mucus (for 10 days), proving the presence of a latent infection. No recurrence of viraemia was observed. The animals were monitored for a further 6 weeks and were consistently shown to be free from infectious virus. Tissues were then obtained postmortem. Co-cultivation of explanted trigeminal ganglia from two out of the four ponies that carried the wild-type virus yielded cultures positive for infectious virus. Apart from nasal epithelium, no infectious virus was recovered from any other tissue. PCR confirmed the presence of virus DNA in the ganglia from all six ponies. Lymphoid tissues also yielded positive signals using this technique. The relevance of virus detection by PCR in lymphoid and neural tissues is discussed in relation to the potential for reactivation of latent virus in the host. However, evidence is presented to show that EHV-1 is neurotropic and, in common with other members of the alpha-herpesvirus subfamily, establishes latency in sensory ganglia from which virus can be reactivated.

Administration, Intranasal↗
PubMed1993

Modulation of the serological response of specific pathogen-free (EHV-free) foals to EHV-1 by previous infection with EHV-4 or a TK-deletion mutant of EHV-1.

EHV-1 was inoculated into specific pathogen-free (SPF) foals in order to study uncomplicated primary responses. Infection resulted in a strong serological response recognizing EHV-1-specific antigens; this contrasts with a previous publication where a weak response was recorded in SPF animals. Antibodies to EHV-1 were readily detected by four techniques (virus neutralization, complement fixation, Western blots and immune precipitation), yet there was comparatively little cross-reaction to EHV-4 target antigen. Re-inoculation with the same virus strain stimulated antibodies to EHV-1 but no additional antigens were recognized and antibodies cross-reacting with EHV-4 antigens were not enhanced. Having characterized the uncomplicated primary response to EHV-1 in SPF foals, further animals were exposed to either EHV-4 or a thymidine kinase-deficient mutant of EHV-1 prior to challenge with w/t EHV-1 to investigate how these infections might modulate the immune responses to EHV-1 or 4. Primary inoculation with EHV-4 or with a thymidine kinase-deficient mutant of EHV-1 produced productive infections as evidenced by virus shedding and pyrexia. In both these cases, however, in contrast to that with w/t EHV-1, the serological response was very weak. Re-infection of foals primed with either EHV-4 or TK-deficient EHV-1 with w/t EHV-1 resulted in a strong response to EHV-1 antigens detected by all four methods. In addition, in the foals given a primary inoculation with EHV-4, superinfection with EHV-1 resulted in a strong cross-reactive response to EHV-4 target antigens. The relevance of these observations to the interpretation of previously reported serological responses to EHVs in SPF and naturally reared animals is discussed.

Animals↗
PubMed1993

A neural network design for event-related potential diagnosis.

Many diseases resulting in neuropsychological impairment show abnormalities by EEG (electroencephalogram) tests. However, EEG analysis is complicated by a wide spectrum of normal patterns. Cerebral evoked potentials are stimulus-induced, averaged EEG potentials that have been found useful in patients with dementing illness. A recent report using the P300 auditory evoked potential shows that simple latency and waveform criteria result in classification accuracy of 65% for multiple sclerosis (MS) patients versus 91% for control subjects. Analysis on the same data set was performed using an artificial neural network (ANN) and a nearest neighbor (NN) classifier. An ANN classifier demonstrated a classification accuracy of 75% versus 87% on MS and control subject groups. Thus prediction accuracy was improved on average, compared with that obtained by NN classifiers or P300 statistical analysis. The classification strategy discovered by a trained ANN was analyzed by a weight pattern analysis method and compared with the P300 latency criteria.

Diagnosis, Computer-Assisted↗
PubMed1993

Regional cerebral blood flow estimation by neural network-based parametric regression analysis.

An artificial neural network (ANN) model was proposed for real-time estimation of regional cerebral blood flow (rCBF), by given head and expired air curves obtained through 133Xe inhalation. The network was constructed according to a regression model described by a linear differential equation. Experimental results compare well with those obtained by conventional curve fitting strategies, but the parameter estimation process is much simplified. A systematic procedure in developing ANN for parametric regression analysis was introduced; networks are constructed according to the selected regression model so that the obtained weights of a trained network directly represent parameters of the regression model which best fits the observed data set. Such a design-oriented methodology extends the classification-based applications of ANN to parametric regression analysis, and therefore may have more generalized applications besides rCBF estimation.

Algorithms↗
PubMed1993

Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals.

Both intranasal (i.n.) and intracerebral (i.c.) inoculation of mice with wild-type equine herpesvirus type 1 (wt EHV-1) caused clinical signs and mortality. Virus could be recovered from target organs (turbinates, lungs and blood) for several days. By contrast, the thymidine kinase (TK)-deficient deletion mutant PR1 produced markedly less clinical disease following both i.n. and i.c. inoculation, and, in particular, no mortality occurred. PR1 did, however, establish productive infections following either route of inoculation. High titres of virus were recovered from target organs although virus did not persist for as long as wt EHV-1 and no viraemia was detected. Primary i.n. infection of mice with either wt EHV-1 or PR1 protected against subsequent challenge with wt EHV-1 5 weeks later. I.n. inoculation of specific pathogen-free (EHV-free) foals with PR1 produced results similar to those observed after infection of mice. Clinical signs were milder than for wt EHV-1 and pyrexia was short-lived or absent. PR1 could be recovered from nasal mucus at high titres but it persisted for only 5 days post-infection compared to 11 days in the case of wt EHV-1. No viraemia was detected in foals infected with PR1. On challenge with wt EHV-1, foals given a primary infection with the mutant were partially protected; but a viraemia with a TK+ EHV-1 was observed. These results demonstrate that our TK- mutant PR1 is markedly less pathogenic than wt EHV-1, despite being able to replicate in the host. The use of TK-deficient mutants of EHV-1 as potential vaccines in the horse is discussed.

Animals↗
PubMed1993

Deoxycorticosterone, 11 beta-hydroxylase and the adrenal cortex.

We report a child in whom DOC excess secondary to congenital adrenal hyperplasia (CAH, 11 beta-hydroxylase deficiency) caused malignant hypertension. Clinical and metabolic control could be achieved only by replacement of both glucocorticoid and mineralocorticoid, thus confirming in clinical practice the hypothesis that DOC is produced from both the zonae fasciculata and glomerulosa of the adrenal cortex under the independent control of the ACTH and renin-angiotensin systems respectively.

Adrenal Cortex↗