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Biomedical subjects

N Walsh

Publications and source records attributed to N Walsh.

At least 19 recordsLinked to original sources
PubMed2001

Merkel cell carcinoma: squamous and atypical fibroxanthoma-like differentiation in successive local tumor recurrences.

Merkel cell carcinoma (MCC) is a rare, frequently lethal, primary neuroendocrine carcinoma of the skin. Histopathologically, it appears as a dermal nodule of small, undifferentiated malignant cells. Historically, MCC was considered to be an eccrine carcinoma. Recognition of its neuroendocrine features later led to the hypothesis that it arose from Merkel cells in the skin, although recent evidence revisits the question of an epithelial origin. We present a case of MCC arising on the temple of a 78-year-old male, in association with an actinic keratosis. Three years later, a local tumor recurrence showed a mixed malignancy comprising small cell neuroendocrine and large cell squamoid components. A further recurrence at the site two years later, after local radiotherapy, revealed a bizarre pleomorphic large cell morphology with retention of immunohistochemical features of a neuroendocrine carcinoma. Evolution to a bizarre pleomorphic large cell neoplasm has been recorded in malignant tumors treated by radiotherapy, but is unique for MCC. The association of this MCC with an actinic keratosis and the development of squamoid differentiation in a local recurrence support the link between MCC and epithelial neoplasia. In addition, its evolution to an atypical fibroxanthoma-like morphology is of interest, because some view atypical fibroxanthomas as bizarre variants of squamous cell carcinoma.

Aged↗
PubMed2001

Effects of oxygen and bFGF on the vulnerability of photoreceptors to light damage.

PURPOSE: To test whether tissue oxygen levels affect the vulnerability of photoreceptors to damage by bright continuous light (BCL). METHODS: Albino rats were raised in standard conditions of cyclic light (12-hour light, 12-hour darkness) with the light level at 5 to 10 lux or 40 to 65 lux. They were then exposed to BCL (1000-1400 lux), either continuously for 48 hours or for the day or night components of the 48-hour period. During BCL, some rats were kept in room air (normoxia, 21% oxygen), some in hypoxia (10%), and some in hyperoxia (70%). Their retinas were examined for cell death, for the expression of basic fibroblast growth factor (bFGF), and for response to light (electroretinogram, ERG). RESULTS: The death of retinal cells induced by BCL was confined to photoreceptors. Within the retina, the severity of death was inversely related to the level of bFGF immunolabeling in the somas of the outer nuclear layer (ONL) before exposure. The death of photoreceptors was accompanied by an upregulation of bFGF protein levels in the ONL and by a decline in the ERG. Both hypoxia and hyperoxia during BCL reduced the photoreceptor death, bFGF upregulation, and ERG decline caused by BCL. The protective effects of hyperoxia and hypoxia were evident during both the day and night halves of the daily cycle. Hypoxia or hyperoxia alone did not upregulate bFGF or ciliary neurotrophic factor (CNTF) expression in the retina. CONCLUSIONS: Photoreceptors are protected from light damage by hypoxia and hyperoxia during exposure. The protection provided by oxygen levels operates during both day and night. The protection is not mediated by an upregulation of bFGF or CNTF.

Animals↗
PubMed2000

Personal medical services. Friends and relations.

Personal medical services pilot schemes remain internally focused. In many areas hospital doctors' willingness to work with general practice has been hampered by chief executives' fear of loss of income. Health authorities have generally failed to take responsibility for the pilot schemes. There are some fears of the schemes creating inequity at local level.

Cooperative Behavior↗
PubMed2000

Primary care. This is your pilot speaking.

An evaluation of 14 personal medical services pilot schemes has found the GPs involved welcome the reduction in paperwork. The flexibility in funding of the schemes has allowed GPs greater leeway in managing their workload. Some of the financial risks of running a practice have been removed. It is questionable whether the schemes are fully using the freedoms envisaged. Some schemes reported a lack of support from their health authority.

Contract Services↗
PubMed2000

Intraretinal axon diameters of a New World primate, the marmoset (Callithrix jacchus).

PURPOSE: Previously, measurements of retinal ganglion cell axon diameter have been used to make inferences about the physiology and clinical pathology of the visual pathway. However, few of these studies were able to unequivocally relate axon diameter to retinal ganglion cell type and other associated measurements. In this and our previous study we have examined intraretinal axon diameters to determine if differences in axon diameter may help to explain conduction velocity measurements found previously. METHODS: Individual retinal ganglion cells of a New World primate, the common marmoset (Collithrix jacchus) were injected iontophoretically with 2% Lucifer yellow and 4% neurobiotin. Labelled cells were visualized by horseradish peroxidase immunohistochemistry and diaminobenzidine and then retinae were mounted vitreal side up on a glass slide. Cell measurements were made with the aid of a camera lucida attachment and computer-aided morphometry Axons were photographed under x 100 oil immersion and measured at a final magnification of x 4600. RESULTS: A sample of 62 parasol cells, 22 midget cells, 16 hedge cells and 11 small bistratified cells were analysed. Dendritic field diameter of the different cell classes showed only moderate (non-significant) increases with eccentricity. Only the parasol cells demonstrated a significant increase in mean axon diameter with eccentricity. When the parasol class was examined more closely, it was found that only parasol cells of the superior, inferior and temporal retina (SIT group) showed significant positive correlations between different cell parameters (mean axon diameter, soma diameter, dendritic field diameter, eccentricity). Soma and dendritic field diameters of the SIT group were significantly larger than those of the nasal parasol cells. However, mean axon diameters of the SIT cells were not significantly different from nasal parasol cells. Axon diameters of nasal parasol cells were very variable and overlapped those of the midget and hedge cell classes to a large extent. CONCLUSIONS: The present data show that for marmoset parasol cells there may not be a clearly defined distinction between nasal and superior, inferior and temporal parasol cells on the basis of axon size. Of particular interest in the present analysis is the clear separation of superior, inferior and temporal parasol cells and nasal parasol cells when comparing soma and dendritic field diameters which is not reflected in the distribution of axon diameters. We suggest that changes in diameter along the length of an axon, differences between retinal quadrants and the variability between cells may be related to minimization of spatiotemporal dispersion necessary for accurate perception of motion within the visual world.

Animals↗
PubMed2000

Total serum cholesterol in relation to psychological correlates in parasuicide.

BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS: To examine the relationship between total serum cholesterol and psychological parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups. RESULTS: Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.

Adolescent↗
PubMed2000

Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover.

Tartrate-resistant acid phosphatase (TRAP) is a secreted product of osteoclasts and a lysosomal hydrolase of some tissue macrophages. To determine whether TRAP expression is rate-limiting in bone resorption, we overexpressed TRAP in transgenic mice by introducing additional copies of the TRAP gene that contained the SV40 enhancer. In multiple independent mouse lines, the transgene gave a copy number-dependent increase in TRAP mRNA levels and TRAP activity in osteoclasts, macrophages, serum, and other sites of normal low-level expression (notably, liver parenchymal cells, kidney mesangial cells, and pancreatic secretory acinar cells). Transgenic mice had decreased trabecular bone consistent with mild osteoporosis. Measurements of the bone formation rate suggest that the animals compensate for the increased resorption by increasing bone synthesis, which partly ameliorates the phenotype. These mice provide evidence that inclusion of an irrelevant enhancer does not necessarily override a tissue-specific promoter.

Acid Phosphatase↗
PubMed2000

Antibiotics for sore throat: impact of feedback to patients on the probability of bacterial infection.

Antibiotics are overused in the management of sore throat. Using a scoring system with 108 attenders, we provided feedback on the likelihood of bacterial infection and measured the impact on initial patient expectation for antibiotic therapy. Patient attitudes and beliefs regarding antibiotics were also examined. Of sixty two patients whose score suggested viral infection, 18(29%) opted not to take an antibiotic prescription. The 42(67%) who still wanted an antibiotic, despite being told it was "unlikely or highly unlikely" to help, had a higher mean attendance rate for sore throat (1.63 v 0.83 (p = 0.14)) and other illness (6.53 v 4.22 (p = 0.22)), and a higher mean re-attendance rate following the study (1.68 v 0.50 (p = 0.025)). Qualitative analysis suggests that this subgroup may believe in the analgesic properties of antibiotics.

Adolescent↗
PubMed1999

Intraretinal axon diameter: a single cell analysis in the marmoset (Callithrix jacchus).

We have labelled individual retinal ganglion cells of a New World primate, the common marmoset (Callithrix jacchus) with neurobiotin and then measured axon, soma and dendritic field diameter. A total of 111 cells were analysed (62 parasol cells, 22 midget cells, 16 hedge cells and 11 small bistratified cells). When all retinal ganglion cells were grouped together axon diameter was positively correlated to soma diameter. When analysed according to cell class only midget cells showed a positive correlation between soma size and mean axon diameter. Dendritic field diameter and mean axon diameter of both parasol and midget cells showed significant correlations. Axon diameter is not constant along the intraretinal length of the axon and the rate of change in diameter appears to be related to the cell class and the initial size of the axon. Midget cell axons showed a rapid increase of up to 20% over the first 200 microm in contrast to parasol cell axons which increased more slowly over this distance but then showed a marked increase in diameter of up to 40% over the next 450 microm. However, axon diameter did not remain at these increased diameters but decreased at greater distances from the soma. The degree to which an axon changes its diameter is related to retinal ganglion cell class and the initial size of the axon. We postulate that these variations in intraretinal axon diameter may have a direct influence on conduction velocity and reflect a compensatory mechanism to minimise spatiotemporal dispersion along the visual pathway.

Animals↗
PubMed1999

Melanosis in association with metastatic malignant melanoma: report of a case and a unifying concept of pathogenesis.

An unusual case of melanosis associated with metastatic malignant melanoma is reported. This was characterized by progressive blue/gray discoloration of the skin of the chest and abdomen in an elderly patient, 1 year after removal of a polypoid malignant melanoma from the right arm. A biopsy of involved skin revealed perivascular aggregates of melanin-laden histiocytes throughout the dermis, the histopathologic hallmark of melanosis. An unusual aspect of the case was the coincidental finding of a tumor embolus within a small dermal vessel, probably a lymphatic. To date, neoplastic melanocytes have been detected in only a small minority of skin biopsies with features of melanosis. This case and a distillation of related information in the literature lead to the conclusion that the essence of melanosis, and the feature that distinguishes this from conventional metastatic melanoma, is the persistent and cumulative dissemination of melanin, via the bloodstream, throughout the body. This in turn leads to progressive pigmentation of all internal organs and the skin. Only continuous access to the circulation by neoplastic melanocytes could explain such a phenomenon. Potential mechanisms by which this could arise are discussed in the context of existing knowledge.

Aged↗
PubMed1999

Total purchasing in primary care: three case studies.

Total purchasing in primary care (TPPC) was piloted in the mid-1990's, first by four "pioneer sites", and later by over 80 first and second waves of "pilot sites". Separate evaluations of three of the pioneers show that they faced challenges similar to those experienced by the pilot sites, namely: the need to develop organisations which were effective both internally and, in their relationships with other health-care agencies, externally; and the difficulties encountered when attempting to change the behaviour of local acute care providers. Although GP fund holding and/or TPPC have had some successes in influencing the pattern of delivery for some elective and community services, the challenge of reducing hospital admissions and lengths of stay remains formidable.

Efficiency, Organizational↗
PubMed1998

Primary care groups. Going through the change.

The successful establishment of primary care groups will demand sensitivity from managers. It is important to acknowledge, and mourn, what is being lost by ending the old arrangements. People do not resist change itself, but the losses and endings it involves. Despite the tight timetable, management should be participative rather than directive.

Administrative Personnel↗
PubMed1998

Spitz nevus versus spitzoid malignant melanoma: an evaluation of the current distinguishing histopathologic criteria.

Because of the well-known difficulty in distinguishing between Spitz nevi and spitzoid malignant melanomas at the microscopic level, the critical importance of this task notwithstanding, expert dermatopathologists across the world have strenuously endeavored to identify histopathologic criteria that would assist microscopists in this effort. Many reports itemizing such criteria are extant. The objective of the current study was to determine which of these criteria serve as the most consistent discriminators. Using a population of 11 spitzoid melanomas and 12 Spitz nevi, we evaluated six sets of criteria purported to be helpful in differentiating between these entities. Overall, we found that six features had significant distinguishing capacity, namely, (1) Kamino bodies, (2) a brisk mitotic rate, (3) mitoses close to the base of the lesion, (4) abnormal mitoses, (5) symmetry, and (6) uniformity of nests from side to side. It is noteworthy that the first three of these rank among the six criteria itemized repeatedly in 50% or more of the sets of criteria evaluated.

Adolescent↗
PubMed1998

Joint care admissions to a psychiatric unit: a prospective analysis.

Despite developments in general hospital liaison psychiatry over the past 20 years, joint care still remains underdeveloped in Europe. Psychiatry continues to move from the mental hospital to the general hospital unit without the parallel evolution of combined medical and psychiatric. An inpatient unit that provides both medical and psychiatric care may provide an essential integration of care that can benefit a select group of patients. The aims of this study were to prospectively evaluate the profile, treatment, and follow-up of patients admitted to the joint-care unit, and to examine the difficulties associated with the treatment of these patients on a joint unit. Eighty-nine patients were admitted to the joint care unit over a 6-month period. Their median length of stay was 2 days (range 1-52 days). Fifty-six (50%) were female. The majority (68) (76%) of the group were admitted following acts of deliberate self-harm. The overall predominant psychiatric diagnosis was depression (41) (46%). During admission, 23 (26%) patients were found to have behavioral and psychiatric problems that were difficult to manage on the ward. Eleven patients caused difficulties for staff relating to the management of their physical illness. Thirty-six (33%) patients were referred for further psychiatric inpatient care from the joint-care unit. The extra burden of these patients' care was felt to fall on the staff working on the psychiatric unit. The joint care unit provided a combined psychiatric and medical service. It was used predominantly by patients following acts of deliberate self-harm. Joint care allowed a comprehensive assessment and initiation of treatment of this patient group as well as a learning experience for medical and nursing staff. The inclusion of such a unit is a worthwhile consideration in any general hospital psychiatric service, with advanced planning easing staff workload.

Acute Disease↗
PubMed1997

Continued thromboxane A2 formation despite administration of a platelet glycoprotein IIb/IIIa antagonist in patients undergoing coronary angioplasty.

Experimental data suggest that formation of thromboxane A2 may be suppressed during administration of a glycoprotein IIb/IIIa antagonist. We determined the dose of one such compound, fradafiban, required to provide > 80% occupancy of the platelet glycoprotein IIb/IIIa and examined its effects on thromboxane A2 formation in patients undergoing PTCA. The dose response to fradafiban and additional effects of aspirin were explored initially in patients with stable coronary artery disease. Fradafiban induced a dose-dependent inhibition of platelet aggregation that correlated with fibrinogen receptor occupancy and plasma drug concentration. Addition of aspirin 300 mg had no effect on these parameters. At the highest dose, mean fibrinogen receptor occupancy was 89.7 +/- 1.2% (n = 3) at 4 hours and platelet aggregation had decreased by 93.4 +/- 2.7%. Eighteen patients undergoing coronary angioplasty were randomized to receive either aspirin 330 mg or that dose of fradafiban producing > 80% fibrinogen receptor occupancy. Platelet aggregation was suppressed throughout the infusion of fradafiban to a greater extent than with aspirin. However, there was a marked increase in urinary excretion of 11-dehydrothromboxane B2 in patients treated with fradafiban: from 1973 +/- 889 to a peak of 9760 +/- 3509 pg/mg creatinine (P = .0046). Despite this evidence of continued platelet activation in vivo, there were no cases of coronary thrombosis. In conclusion, fradafiban suppresses platelet aggregation and may be a useful alternative to aspirin in the prevention of thrombotic events in patients undergoing PTCA. However, there is continued formation of thromboxane A2, which may continue to exert its effects as a potent vasoconstrictor and vascular smooth muscle mitogen.

Administration, Oral↗
PubMed1997

High definition 3D ultrasound imaging.

We have demonstrated high definition and improved resolution using a novel scanning system integrated with a commercial ultrasound machine. The result is a volumetric 3D ultrasound data set that can be visualized using standard techniques. Unlike other 3D ultrasound images, image quality is improved from standard 2D data. Image definition and bandwidth is improved using patent pending techniques. The system can be used to image patients or wounded soldiers for general imaging of anatomy such as abdominal organs, extremities, and the neck. Although the risks associated with x-ray carcinogenesis are relatively low at diagnostic dose levels, concerns remain for individuals in high risk categories. In addition, cost and portability of CT and MRI machines can be prohibitive. In comparison, ultrasound can provide portable, low-cost, non-ionizing imaging. Previous clinical trials comparing ultrasound to CT were used to demonstrate qualitative and quantitative improvements of ultrasound using the Sandia technologies. Transverse leg images demonstrated much higher clarity and lower noise than is seen in traditional ultrasound images. An x-ray CT scan was provided of the same cross-section for comparison. The results of our most recent trials demonstrate the advantages of 3D ultrasound and motion compensation compared with 2D ultrasound. Metal objects can also be observed within the anatomy.

Computer Simulation↗