Search PubMed⌕ Search

Biomedical subjects

R Howard

Publications and source records attributed to R Howard.

At least 37 records · Page 2Linked to original sources
PubMed1996

Auditory hallucinations inhibit exogenous activation of auditory association cortex.

Percepts unaccompanied by a veridical stimulus, such as hallucinations, provide an opportunity for mapping the neural correlates of conscious perception. Functional magnetic resonance imaging (fMRI) can reveal localized changes in blood oxygenation in response to actual as well as imagined sensory stimulation. The safe repeatability of fMRI enabled us to study a patient with schizophrenia while he was experiencing auditory hallucinations and when hallucination-free (with supporting data from a second case). Cortical activation was measured in response to periodic exogenous auditory and visual stimulations using time series regression analysis. Functional brain images were obtained in each hallucination condition both while the patient was on and off antipsychotic drugs. The response of the temporal cortex to exogenous auditory stimulation (speech) was markedly reduced when the patient was experiencing hallucinating voices addressing him, regardless of medication. Visual cortical activation (to flashing lights) remained normal over four scans. From the results of this study and previous work on visual hallucinations we conclude that hallucinations coincide with maximal activation of the sensory and association cortex, specific to the modality of the experience.

Acoustic Stimulation↗
PubMed1996

Mucins in airway secretions from healthy and chronic bronchitic subjects.

Little is known about whether the properties of respiratory mucins are altered as a result of airway irritation, but histochemical studies of respiratory tract secretory cells show a more 'acidic' staining pattern after exposure to tobacco smoke. Furthermore it has been suggested that proteoglycans are the major glycoconjugates in 'normal' respiratory secretions, whereas mucins predominate in sputum. To investigate these observations further, mucins from secretions collected from the tracheal surface of healthy non-smoking 'normal' subjects and sputum from patients with chronic bronchitis were compared. All samples contained one major mucin population after density-gradient centrifugation, and a small amount of 'denser' mucin was present in some chronic bronchitic and one of the 'normal' samples. Proteoglycans were not a major component of 'normal' secretions. The major mucin population from chronic bronchitic samples had molecular masses between 10 and 30 MDa and behaved as random coils in solution. Whole mucins from 'normal' individuals and chronic bronchitic patients were excluded from Sepharose CL-2B, whereas reduced subunits were included. Proteolysis of subunits yielded two populations of high-molecular-mass glycopeptides differing in size, suggesting the presence of two different tandem repeat regions in the mucins. Finally, mucins from patients with chronic bronchitis are less, rather than more, acidic than those from 'normal' individuals. Mucins from bronchitic sputum and 'normal' secretions are thus similar in their macromolecular properties, but differ slightly in charge density.

Adolescent↗
PubMed1996

Statistical methods of estimation and inference for functional MR image analysis.

Two questions arising in the analysis of functional magnetic resonance imaging (fMRI) data acquired during periodic sensory stimulation are: i) how to measure the experimentally determined effect in fMRI time series; and ii) how to decide whether an apparent effect is significant. Our approach is first to fit a time series regression model, including sine and cosine terms at the (fundamental) frequency of experimental stimulation, by pseudogeneralized least squares (PGLS) at each pixel of an image. Sinusoidal modeling takes account of locally variable hemodynamic delay and dispersion, and PGLS fitting corrects for residual or endogenous autocorrelation in fMRI time series, to yield best unbiased estimates of the amplitudes of the sine and cosine terms at fundamental frequency; from these parameters the authors derive estimates of experimentally determined power and its standard error. Randomization testing is then used to create inferential brain activation maps (BAMs) of pixels significantly activated by the experimental stimulus. The methods are illustrated by application to data acquired from normal human subjects during periodic visual and auditory stimulation.

Acoustic Stimulation↗
PubMed1996

Movement-related effects in fMRI time-series.

This paper concerns the spatial and intensity transformations that are required to adjust for the confounding effects of subject movement during functional MRI (fMRI) activation studies. An approach is presented that models, and removes, movement-related artifacts from fMRI time-series. This approach is predicated on the observation that movement-related effects are extant even after perfect realignment. Movement-related effects can be divided into those that are a function of position of the object in the frame of reference of the scanner and those that are due to movement in previous scans. This second component depends on the history of excitation experienced by spins in a small volume and consequent differences in local saturation. The spin excitation history thus will itself be a function of previous positions, suggesting an autoregression-moving average model for the effects of previous displacements on the current signal. A model is described as well as the adjustments for movement-related components that ensue. The empirical analyses suggest that (in extreme situations) over 90% of fMRI signal can be attributed to movement, and that this artifactual component can be successfully removed.

Artifacts↗
PubMed1996

Drug treatment of schizophrenia and delusional disorder in late life.

As people live longer, an increasing proportion of patients with schizophrenia and delusional disorder will be elderly. Little has been published on treatment response, effective treatment strategies, or the use of atypical neuroleptics in this group. This review of the literature explores documented response rate, route and dose of neuroleptic, indicators of poor response, and the use of novel drugs. Despite great variation in the neuroleptic dose ranges employed, patients with late-onset disease often continue to experience psychotic symptoms. Compliance with treatment is the most important determinant of outcome. Atypical neuroleptics are specifically indicated for patients with visual hallucinations or extrapyramidal symptoms. Elderly psychotic patients should be treated as vigorously and with as wide a range of neuroleptics as their younger counterparts. Physicians should not restrict drug doses to modest levels in all cases as long as patients are monitored frequently for the emergence of side effects.

Aged↗
PubMed1996

Brefeldin A effects in plant and fungal cells: something new about vesicle trafficking?

Whilst the function and organization of the secretory machinery in eukaryotic cells exhibit basic similarities, the compartmentation of the endomembrane system can show significant differences between the fungal, plant and animal kingdoms. The use of the antibiotic brefeldin A (BFA) as an inhibitor of secretion in both animal and yeast cells has resulted in a remarkable advance in our understanding of the modes of action of vesicle shuttles between the endoplasmic reticulum and Golgi apparatus and within the Golgi apparatus itself. It is now apparent that application of the drug to filamentous fungi and plants will also help unravel the workings of the secretory system in these organisms. In this paper we review recent progress in our laboratories on elucidating the effects of BFA on the morphology of the Golgi apparatus and compare these with recently published data on fungal and plant cells. Variation in the response to BFA are reported, which may not all be attributed to differences in drug concentration and time of treatment. These may reflect differences in cellular sensitivity or multiple sites of action of the drug, and the existence of a specific molecular target for BFA is questioned.

Biological Transport↗
PubMed1996

Comparison of caudal bupivacaine and diamorphine with caudal bupivacaine alone for repair of hypospadias.

Forty-five boys undergoing repair of hypospadias were allocated randomly to one of two groups. After induction of anaesthesia, 22 patients received 0.25% caudal bupivacaine 0.5 ml kg-1 and diamorphine 30 micrograms kg-1 and the remaining 23 patients received 0.25% caudal bupivacaine 0.5 ml kg-1 alone. Pain scores (Children's Hospital of Eastern Ontario Pain Scale), sedation scores, ventilatory frequency, analgesic requirements and associated side effects were recorded for the first 24 h after operation. The two groups were indistinguishable in age, weight and duration of surgery. There was a statistically significant reduction in early pain scores. There was also a statistically significant increase in the time to first passage of urine in those boys in the diamorphine group who were not catheterized during operation.

Analgesics, Opioid↗
PubMed1996

Detection of coccidioidal antibodies by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera from patients evaluated for coccidioidomycosis.

During a 9-month study of patients being evaluated for coccidioidomycosis, 1 or more serum samples were obtained from 138 patients with an illness suggestive of recent infection. In this group, standard immunodiffusion tests of unconcentrated sera were positive for 25; 49 additional patients had at least 1 reactive test result by newer enzyme-linked serologic tests. At least 11 of these 49 patients had coccidioidomycosis as determined by culture or subsequent standard serologic tests. Patients with coccidioidomycosis identified only by newer tests had fewer or milder clinical abnormalities than did patients in whom the disease was detected by standard tests. For 31 other patients with illness of a chronic or undetermined duration, newer tests detected only 10 more than the 18 identified by standard tests, suggesting that later in the course of illness, standard testing gains in sensitivity for coccidioidal infection.

Antibodies, Fungal↗
PubMed1996

A comparison of the induction characteristics of sevoflurane and halothane in children.

The induction characteristics of sevoflurane and halothane were compared in 81 children aged 6 months to 6 years. The mean time taken to achieve loss of eyelash reflex was significantly shorter with sevoflurane than with halothane (sevoflurane, mean time (SD) 1 min 41 s (35 s), halothane, mean time (SD) 2 min 17 s (43 s), t = 4.11, p = < 0.01). The mean time taken to complete induction (to achieve steady spontaneous ventilation and small pupils with central gaze) was also shorter in children induced with sevoflurane (sevoflurane, mean time (SD) 3 min 58 s (1 min 8 s), halothane, mean time (SD) 4 min 50 s, (1 min 27 s), t = 2.29, p = 0.027). Effects on heart rate, blood pressure and oxygen saturation during induction were similar for both agents. There were no major complications during induction with either halothane or sevoflurane.

Anesthesia, Inhalation↗
PubMed1996

A comparison of the recovery characteristics of sevoflurane and halothane in children.

The recovery characteristics of sevoflurane and halothane anaesthesia were compared in 40 children aged 6 months to 6 years undergoing day case surgery. The mean time taken to open eyes after surgery had ended was appreciably and significantly shorter after sevoflurane than after halothane (sevoflurane, mean time (SD) 7 min 52 s (5 min 46 s), halothane, mean time (SD) 15 min 50 s (9 min 2 s), t = 3.32, p = 0.002). The time taken to be ready for discharge from the recovery unit to the ward was also significantly shorter after sevoflurane than after halothane (sevoflurane, mean time (SD) 12 min 46 s (4 min 11 s), halothane, mean time (SD) 19 min 13 s (9 min 48 s), t = 2.7, p < 0.01). However, more children were in pain and given analgesia after sevoflurane (p < 0.01) and the mean time to reach the criteria for discharge home was similar in both groups (sevoflurane, mean time (SD) 2 h 9 min (17 min), halothane, mean time (SD) 2 h 4 min (8 min)). There were no major complications in either group.

Ambulatory Surgical Procedures↗
PubMed1996

Identification of mutations in the Ki-ras gene in human retinoblastoma.

PURPOSE: To investigate the mutational status of the Ki-ras gene in retinoblastoma and to evaluate a correlation of the genotype with clinical and histopathologic variables. METHODS: Tumor samples were microdissected from sectioned archival paraffin-embedded tissue. Ki-ras genomic sequences (exons 1 and 2) were amplified by polymerase chain reaction then analyzed by single-strand conformation polymorphism and direct sequencing. Tissue sections, flanking the analyzed samples, were stained with hematoxylin and eosin for examination by light microscopy. RESULTS: Four of 12 tumors had mutation in exon 1, codon 12 of the Ki-ras gene; none had mutation in exon 2. Signal intensity of the mutated alleles indicates clonal mutation in the tumor cell populations. One of four bilateral tumors was mutated, and all three samples with undifferentiated histologic appearance harbored a clonal Ki-ras mutation. However, only one of nine moderately to poorly differentiated tumors harbored a mutation. CONCLUSIONS: Ki-ras, an oncogene seldom altered in neuroectodermal neoplasms, is mutated in one third of the retinoblastomas studied. The Ki-ras mutations are clonal, suggesting that affected cells have a selective growth advantage. The mutations are present and are likely to play a pathogenetic role in heritable and sporadic retinoblastomas. These results suggest that mutations in Ki-ras are preferentially associated with undifferentiated tumors.

Adolescent↗
PubMed1995

White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly.

We determined the prevalence and anatomical location of areas of white matter hyperintensity visualized by magnetic resonance imaging in the brains of 38 late paraphrenic patients with an onset of psychotic illness after the age of 60 and 31 healthy aged community volunteers. All degrees of white matter signal hyperintensity were very common in both groups, and there was no excess of such changes in the brain of patients. Periventricular white matter and subcortical grey matter hyperintensities were significantly associated with both measured diastolic and systolic blood pressure in patients and control subjects. Periventricular and deep white matter, together with subcortical grey matter hyperintensities, were significantly associated with increased age. The excess of such presumed brain-imaging abnormalities previously reported in patients with an onset of psychosis late in life may be a consequence of earlier authors' failure to include examination of appropriate community control populations and to carefully exclude patients with evidence of stroke.

Aged↗
PubMed1995

Increasing age is a risk factor for psychosis in the elderly.

We examined the association between ageing and the administrative incidence rate of late onset (after age 59) non-organic, non-affective psychosis in two samples of patients aged 60 years or older who were first admitted to hospital in (1) The Netherlands between 1978 and 1992 (n = 8010) and (2) nine regional health authorities in England and Wales (n = 1777) between 1976 and 1978. There was a linear trend in the association between increasing age and first admission rates for non-organic, non-affective psychosis in the elderly, after adjustment for the possible confounding effects of time trend and gender, corresponding to an 11% increase in the incidence with each 5-year increase in age. These observations support a connection between degenerative brain processes and onset of non-affective psychosis in the elderly.

Aged↗
PubMed1995

Tinea capitis: new perspectives on an old disease.

Tinea capitis caused by Trichophyton tonsurans is a common infection in children, and has become a significant public health problem in the United States. Epidemics of tinea capitis occur both in families and in institutions such as schools and day care centers. Infection is often difficult to eradicate. Fomites and asymptomatic carriers likely contribute to the spread of the disease and to re-infection of treated patients. The morphology of tinea capitis is diverse, from seborrhea-like scaling to tender, inflammed nodules on the scalp. Because a lengthy course of systemic griseofulvin is required to treat this infection, management of tinea capitis can be challenging. As newer antifungal agents are developed, more effective and convenient therapy for tinea capitis may become available.

Adult↗
PubMed1995

Magnetic resonance imaging volumetric measurements of the superior temporal gyrus, hippocampus, parahippocampal gyrus, frontal and temporal lobes in late paraphrenia.

Quantified magnetic resonance measurements were made of superior temporal gyrus, parahippocampal gyrus, hippocampal, frontal and temporal lobe volumes and of the planar area of the thalamus and basal ganglia structures in 47 late paraphrenic patients and 33 healthy elderly controls. The late paraphrenics were divided into 31 schizophrenics and 16 patients with delusional disorder according to ICD-10 guidelines. Patients with delusional disorder tended to have smaller left temporal volumes compared with control subjects and patients with schizophrenia, but this difference failed to reach accepted levels of statistical significance after correction for the effects of multiple statistical comparisons, age and total brain size. Physiological right-left asymmetry, reported for temporal and frontal lobe volumes, was present in control, schizophrenic and delusional disorder subjects but delusional disorder patients had a significantly greater degree of temporal lobe asymmetry. The results add to the evidence for heterogeneity among late-onset psychoses and emphasize the subtle nature of any structural brain abnormalities in these patients.

Aged↗
PubMed1995

Treatment-resistant depression in the elderly.

Apparent treatment-resistant depression (TRD) is frequently encountered by and poses particular challenges for the old-age psychiatrist. The prevalence of true nonresponse to treatment is not known with accuracy but reports put it at 18% to 40% for the elderly. This article reviews the concept of TRD in the elderly, discussing the factors involved in apparent resistance and the treatment of this group. We suggest that absolute TRD may be a rarer entity than the estimated 18% to 40% if depressed patients are treated carefully and vigorously.

Aged↗
PubMed1995

Impact of childhood cancer on siblings and family: family strategies for primary health care.

The article reviews the impact of a chronic illness with a potentially life-threatening outcome on siblings and suggests strategies to enhance sibling support by an advanced practice nurse. The well siblings in the family system have the potential to perceive threatened or actual losses as a result of their brother's or sister's illness. The importance of considering total family structure, including the sibling's emotional needs, in an ongoing assessment to determine strengths, vulnerabilities, and coping abilities is presented. The advanced practice nurse in an ambulatory care setting, community setting, or hospital is in a unique position to provide comprehensive guidance and coordination of mechanisms of support in concert with the family in an effort to reduce vulnerability and to maintain the emotional well-being of the siblings.

Adaptation, Psychological↗