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Biomedical subjects

N Pugh

Publications and source records attributed to N Pugh.

At least 19 recordsLinked to original sources
PubMed2006

The functional anatomy of Kager's fat pad in relation to retrocalcaneal problems and other hindfoot disorders.

Kager's fat pad is a mass of adipose tissue occupying Kager's triangle. By means of a combined magnetic resonance imaging, ultrasound, gross anatomical and histological study, we show that it has three regions that are closely related to the sides of the triangle. Thus, it has parts related to the Achilles and flexor hallucis longus (FHL) tendons and a wedge of fat adjacent to the calcaneus. The calcaneal wedge moves into the bursa during plantarflexion, as a consequence of both an upward displacement of the calcaneus relative to the wedge and a downward displacement of the wedge relative to the calcaneus. During dorsiflexion, the bursal wedge is retracted. The movements are promoted by the tapering shape of the bursal wedge and by its deep synovial infolds. Fibrous connections linking the fat to the Achilles tendon anchor and stabilize it proximally and thus contribute to the motility of its tip. We conclude that the three regions of Kager's fat pad have specialized functions: an FHL part which contributes to moving the bursal wedge during plantarflexion, an Achilles part which protects blood vessels entering this tendon, and a bursal wedge which we suggest minimizes pressure changes in the bursa. All three regions contribute to reducing the risk of tendon kinking and each may be implicated in heel pain syndromes.

Achilles Tendon↗
PubMed2005

Review of the vascularisation of the human Achilles tendon.

A region of avascularity mid-way along the length of the Achilles tendon has long been associated with rupture. Whilst it is agreed that this region is the location most common to rupture, the exact vascular distribution appears unclear. Regions of avascularity identified within the tendon have included the origin and insertion, as well as the midsection. This review aims to analyse critically and summarise all previous studies of the vascularisation of the healthy human Achilles tendon, in order to determine the most likely region of avascularity and, thereby establish whether a relationship exists between vascularisation and rupture. Whilst no definitive conclusion was reached, it was concluded that the vascularisation does affect the tensile strength and so rupture vulnerability of the healthy Achilles tendon, although it is unlikely to be either the sole, or most significant, contributor. Other factors, such as thinning and twisting of the tendon at the midsection are mechanical influences that will increase the incidence of rupture by increasing the concentration of stress.

Achilles Tendon↗
PubMed2001

Quantification of power Doppler energy and its future potential.

OBJECTIVE: To test a new software package (Color Quantifier, Kinetic Imaging, Liverpool, United Kingdom) that quantifies power Doppler energy and to determine its reproducibility. DESIGN: Intraobserver and interobserver reproducibility study. SETTING: University tertiary referral center. PATIENT(S): Transvaginal power Doppler ultrasound images were recorded from women taking part in a study evaluating the physiological vascular changes in the uterus and ovaries during the normal menstrual cycle. INTERVENTION(S): Nineteen consecutive frames of regions of interest in the uterus, ovary, and follicle, respectively, were analyzed by each of four observers on 10 occasions. MAIN OUTCOME MEASURE(S): Analysis of variance to determine the image and observer effect as well as the intraobserver and interobserver coefficients of variation. RESULT(S): Significant image and observer effects were found. However, the image effect was by far the largest component of the total variation. The large image-to-image variability was expected because the cardiac cycle was included within the 19 frames (images) analyzed. The combined intraobserver and interobserver variation, expressed as the coefficients of variation, was found to be small for the above indices (as low as 1.9%), particularly for total ovary and endometrium. CONCLUSION(S): The indices obtained with this color quantification software are reproducible in an in vitro setting using prerecorded images. Its applicability as a useful assay in the clinical setting requires further evaluation.

Analysis of Variance↗
PubMed2001

Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity.

We have characterized a new immunostimulatory polysaccharide called Aloeride from commercial aloe vera (Aloe barbadensis) juice. Aloeride is between 4 and 7 million Da, and its glycosyl components include glucose (37.2%), galactose (23.9%), mannose (19.5%), and arabinose (10.3%). At 0.5 microg/mL Aloeride increased NF-kappa B directed luciferase expression in THP-1 human monocytic cells to levels 50% of those achieved by maximal concentrations (10 microg/mL) of LPS. Aloeride induced the expression of the mRNAs encoding IL-1beta and TNF-alpha to levels equal to those observed in cells maximally activated by LPS. Acemannan, the major carbohydrate component from aloe, used at 200 microg/mL in the macrophage assay resulted in negligible NF-kappa B activation. Analysis of acemannan and Aloeride using size-exclusion chromatography suggests that the low activity of acemannan is due to trace amounts of Aloeride. Although Aloeride comprises only 0.015% of the aloe juice dry weight, its potency for macrophage activation accounts fully for the activity of the crude juice.

Adjuvants, Immunologic↗
PubMed2001

Isolation of three high molecular weight polysaccharide preparations with potent immunostimulatory activity from Spirulina platensis, aphanizomenon flos-aquae and Chlorella pyrenoidosa.

This research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade microalgae that are potent activators of human monocytes/macrophages: "Immulina" from Spirulina platensis, "Immunon" from Aphanizomenon flos-aquae, and "Immurella" from Chlorella pyrenoidosa. These polysaccharides are structurally complex and have estimated molecular weights above ten million daltons. All three polysaccharides are highly water soluble and comprise between 0.5 % and 2.0 % of microalgal dry weight. Immunostimulatory activity was measured using a transcription factor-based bioassay for nuclear factor kappa B (NF-kappa B) activation in THP-1 human monocytes/macrophages. Using this system the EC(50) values for these microalgal polysaccharides are between 20 and 110 ng/ml (about 10pM). THP-1 activation was confirmed by measuring immune cytokine mRNA induction using reverse transcriptase-polymerase chain reaction (RT-PCR). Each polysaccharide substantially increased mRNA levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). These polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.

Adjuvants, Immunologic↗
PubMed2001

Characterization of human monocyte activation by a water soluble preparation of Aphanizomenon flos-aquae.

Aphanizomenon flos-aquae (AFA) is a fresh-water microalgae that is consumed as a nutrient-dense food source and for its health-enhancing properties. The current research characterizes the effect of a water soluble preparation from AFA on human monocyte/macrophage function and compares the effect of AFA with responses from known agents that modulate the immune system. At 0.5 pg/ml the AFA extract robustly activated nuclear factor kappa B (NF-kappa B) directed luciferase expression in THP-1 human monocytic cells to levels at 50% of those achieved by maximal concentrations (10 microg/ml) of bacterial lipopolysaccharide (LPS). In addition, the AFA extract substantially increased mRNA levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and enhanced the DNA binding activity of NF-kappa B. The effects of AFA water soluble preparation were similar to the responses displayed by LPS, but clearly different from responses exhibited by tetradecanoyl phorbol acetate (TPA) and interferon-gamma (INF-gamma). Pretreatment of THP-1 monocytes with factors known to induce hyporesponsiveness suppressed both AFA-dependent and LPS-dependent activation. These results suggest that the macrophage-activating properties of the AFA water soluble preparation are mediated through pathways that are similar to LPS-dependent activation.

Cell Extracts↗
PubMed2001

Podophyllotoxin lignans enhance IL-1beta but suppress TNF-alpha mRNA expression in LPS-treated monocytes.

There exists a growing body of research which indicates that antimitotics such as taxol and colchicine influence cytokine gene expression. In the present study we examined the effect of podophyllotoxin and six analogs on nuclear factor kappa B (NF-kappa B) activation, and on interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression in human THP-1 monocytes. All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin. The remaining three analogs (podophyllotoxin-4-O-glucoside, beta-peltatin-beta-D-glucopyransoide and 1,2,3,4-dehydrodesoxypodophyllotoxin) were inactive. Clearly certain structural features such as the presence of a glycosidic group or ring aromatization results in loss of biological activity. Interestingly, the analogs that were inactive in our assays have also been previously shown to lack affinity for tubulin binding. These results suggest that during the initial hours of exposure to podophyllotoxin or specific analogs these compounds do not act as independent stimulants of human monocyte activation, but can selectively enhance or suppress LPS-induced cytokine gene expression.

Cells, Cultured↗
PubMed2000

Is there carotid artery aneurysm formation following saphenous vein patch endarterectomy?

The use of saphenous vein patching following carotid endarterectomy is reported to produce aneurysmal dilatation with the risk of thrombosis and possible rupture. The authors have studied patients who have had saphenous vein patch angioplasty following carotid endarterectomy to assess whether there is any progressive arterial dilatation. Thirty-five patients who had undergone saphenous vein patch carotid endarterectomy were age- and sex-matched with 31 subjects that had direct closure endarterectomy. All participants underwent carotid duplex scanning. The external diameters of the mid common carotid artery, the bulb and the proximal internal carotid artery were measured bilaterally. The diameters of the endarterectomized carotid were compared with the contralateral side using a paired t-test. Using an unpaired t-test, the saphenous vein angioplasty group was compared with the directly closed group. A graph was plotted of the ratio of internal carotid artery diameter of the saphenous vein angioplasty group (endarterectomized artery to the contralateral artery) against the length of follow-up, and the Pearson correlation coefficient was calculated. When the saphenous vein angioplasty group was compared with the directly closed group there was a significant difference between the carotid bulb (11.6 versus 9.7mm, P < 0.001) and internal carotid artery diameters (9.0 versus 7.0mm, P < 0.001). Longitudinal analysis of the saphenous vein angioplasty group showed that the increased diameter of the endarterectomized internal carotid artery progressed with time after surgery (r = 0.51, P < 0.005, and r = 0.56, P < 0.001). Vein patching increases the diameter of the internal carotid artery, and this may further increase with time possibly predisposing to aneurysm formation. Further longitudinal studies of paired data are required.

Adult↗
PubMed2000

Immunostimulatory effects of cycloartane-type triterpene glycosides from astragalus species.

In the course of our research on the oligoglycosidic constituents of Turkish Astragalus species, we have isolated a number of cycloartane-type triterpene glycosides. The current study examines the immunostimulatory effects of nineteen of these cycloartane-type compounds using a transcription-based bioassay for Nuclear Factor kappa B (NF-kappaB) activation in a human macrophage/monocyte cell line, THP-1. All compounds were inactive at 100 microg/ml except astragaloside I which increased NF-kappaB directed luciferase expression to levels about 65% as compared with maximal stimulation by E. coli lipopolysaccharide (LPS) at 10 microg/ml. None of the compounds were active at low dosage levels (0.1 microg/ml) in combination with 50 ng/ml LPS. Astragaloside I also increased mRNA expression of the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as measured using reverse transcriptase-polymerase chain reaction (RT)-PCR. Based on these results it is clear that certain structural features are required for immunostimulation of cycloartane-type triterpene glycosides.

Adjuvants, Immunologic↗
PubMed1999

A vascular basis for repetitive strain injury.

OBJECTIVE: The blanket term 'repetitive strain injury' (RSI) covers a wide variety of work-related clinical syndromes, most of which are localized lesions. However, some patients complain of diffuse forearm pain, a clinically distinct form of RSI, the aetiology of which is unknown. METHODS: Using Doppler ultrasound, we measured the vascular responses to muscular work in the radial artery in 13 patients with bilateral diffuse forearm pain, seven with unilateral diffuse pain and 19 controls with localized arm pain. RESULTS: We found that in diffuse forearm pain the radial artery is relatively constricted compared to the controls and fails to vasodilate with exercise, which suggests that diffuse forearm pain may be due to physiological claudication of the working forearm muscle. CONCLUSION: A possible explanation is inhibition of local endothelial nitric oxide function, and this may be an unusual secondary, but self-perpetuating, pain condition which can follow other more specific, but chronic, arm pain syndromes in susceptible individuals.

Adolescent↗
PubMed1996

The influence of total knee arthroplasty on lower limb blood flow.

Ischaemic complications of total knee arthroplasty (TKA) are unusual and tend to occur in patients with peripheral vascular disease (PVD). A prospective study was undertaken to investigate the effect of TKA on blood flow in patients without clinical evidence of PVD. Ankle brachial index (ABI) did not alter post-operatively and no changes in arterial waveforms were found. Unless there is clinical evidence of PVD, TKA under tourniquet control is therefore very unlikely to cause ischaemic complications.

Aged↗
PubMed1996

Colour-coded duplex assessment alone before carotid endarterectomy.

This study assessed whether carotid colour-coded duplex imaging can provide sufficient information to investigate patients before carotid endarterectomy. One hundred patients with symptomatic carotid artery disease (amaurosis fugax 24, transient ischaemic attack 38 and established stroke 38) were assessed by both colour-coded duplex imaging and arch angiography. Stenoses were graded at angiography using the linear method from the European Carotid Surgery Trial and on duplex using peak systolic velocity criteria. Angiograms were also analysed for any arch or intracerebral pathology which would alter surgical management. In defining 70-99 per cent stenoses, duplex had a sensitivity of 98 per cent, specificity 96 per cent, positive predictive value of 96 per cent, negative predictive value 98 per cent and accuracy 97 per cent compared with angiography for both symptomatic and asymptomatic carotids (chi 2 = 1.22, 1 d.f., P = 0.25). With respect to the symptomatic carotid arteries angiography gave different information from duplex in six patients (6 per cent): definition of 70-99 per cent carotid stenosis was different (four), visualization was poor on duplex (one) and an intracerebral aneurysm was identified by angiography. One patient died following arch angiography as a result of mesenteric thrombosis. Carotid duplex imaging alone would appear to be sufficient to assess most patients before carotid endarterectomy as an accurate, safe and relatively cheap investigation compared with angiography. In cases where duplex assessment does not allow full visualization of the carotid bifurcation angiography is required.

Adult↗
PubMed1995

Blood flow in breast cancer and fibroadenoma estimated by colour Doppler ultrasonography.

Blood flow was measured by colour Doppler ultrasonography in 33 fibroadenomas of size 5-31 mm and 28 malignant breast masses of 8-37 mm visible on ultrasonography. There was detectable blood flow in 11 fibroadenomas and 21 cancers (P < 0.01). The median peak systolic frequency was 1.0 (range 0.25-2.0) kHz in malignant tumours and 0.5 (range 0.2-1.25) kHz in fibroadenomas. Blood flow was not detected in the eight fibroadenomas of less than 13 mm but was present in five of seven cancers smaller than this. Five of six carcinomas with three or more detectable vessels were classified as grade III on histological examination, compared with two of 11 carcinomas with one or two vessels. Similarly, five of seven cancers with three or more detectable vessels had axillary lymph node metastases compared with two of 13 with only one or two vessels. Detectable blood flow in breast masses is more common in cancer than in fibroadenoma and is highly suggestive of malignancy if the mass is less than 13 mm in size. Malignant tumours with a larger number of vessels are more likely to be of high grade and to have associated axillary node metastases.

Adolescent↗
PubMed1995

Flush saphenofemoral ligation and multiple stab phlebectomy preserve a useful greater saphenous vein four years after surgery.

PURPOSE: Flush saphenofemoral ligation, with multiple cosmetic stab phlebectomy, successfully treats saphenofemoral reflux and superficial varicosities. The long-term effect on the residual greater saphenous vein (GSV) requires evaluation. METHODS: Noninvasive triplex ultrasound assessment of the residual GSV for potential use as a vein graft was used. We evaluated the independent objective and subjective cosmetic outcomes. We also used analysis to determine the correlation between GSV reflux, symptoms, and cosmetic outcome. RESULTS: Seventy-two limbs were assessed at a median follow-up of 4 years (interquartile range 3 to 5 years). Fifty-nine limbs had patent GSVs above and below the knee. The mean length patent was 51 cm, and the mean internal diameters above and below the knee were 3.6 and 2.8 mm, respectively. In 65% of cases the vein had suitable ultrasonic characteristics, suggesting that it would be suitable for use as a conduit for a vascular bypass graft. Sixty-two limbs were considered a symptomatic success and 61 an objective cosmetic success. There was no correlation between the symptomatic and cosmetic outcome and the presence of superficial GSV reflux (linear regression analysis). CONCLUSIONS: These findings support the effectiveness of the procedure of flush saphenofemoral ligation and multiple stab phlebectomy with regard to cosmetic and symptomatic outcome and may preserve the GSV for use as an autologous bypass graft.

Esthetics↗
PubMed1995

Management of advanced cervical metastasis using intraoperative radiotherapy.

Seventy-five patients who had advanced cervical metastasis with possible invasion of the deep muscles or carotid artery were approached with aggressive resection and intraoperative radiotherapy (IORT). All metastatic nodes were greater than 3 cm, 65% were fixed on clinical examination, and 35% involved the carotid artery. Forty-six (61%) of the patients had previously received irradiation. Fifteen of the patients required extended neck dissections with carotid resections and grafting. After the resection an average single dose of 2000 cGy of electron beam IORT was delivered. At 2 years, the local control rate within the IORT port was 68% and the absolute survival rate was 45%. Local control rates for close and microscopic margins (76% and 73%, respectively) were significantly better than the control rate for gross residual disease (25%, P < .05). The combination of extended neck dissection, including carotid artery resection if necessary, and IORT appears to offer improved control.

Carcinoma, Squamous Cell↗
PubMed1993

An assessment of the long saphenous vein for potential use as a vascular conduit after varicose vein surgery.

PURPOSE: There is controversy in the surgical management of varicose veins between stripping of the long saphenous vein (LSV) and high ligation. Moreover, preservation of the LSV is desirable for future coronary or peripheral artery bypass. We have studied 75 limbs in 44 patients after high saphenous ligation with multiple stab phlebectomy. METHODS: Subjective assessment of the outcome of surgery was made with a linear analog scale, and objective cosmetic outcome was assessed by an independent observer (LF) who had not been involved in the surgical treatment of these patients with our modification from the criteria first described by Jakobsen. Patency, length, and diameter of the LSV was measured 6 to 14 months (mean 12 months) after operation with a duplex scanner and a color-flow scanner. Valvular incompetence in the LSV and perforators was also assessed. RESULTS: Results show a good subjective and objective outcome in 95% and 97% of limbs, respectively. The LSVs were patent from ankle to groin in 68% and from ankle to knee in 82%, with a mean diameter of 4.0 +/- 0.1 mm (mean +/- SEM). There was no statistically significant difference in symptomatic outcome and presence of reflux in the LSV (X2 = 0.465; p = 0.4954; NS) or objective cosmetic outcome and the presence of reflux in the LSV (chi 2 = 2.916; p = 0.0877; NS). CONCLUSIONS: It is concluded that high saphenofemoral ligation combined with multiple "stab avulsions" preserves an LSV with characteristics suggesting suitability for future use as a vascular prosthesis with good early symptomatic and cosmetic results.

Esthetics↗