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Biomedical subjects

S J McPherson

Publications and source records attributed to S J McPherson.

18 recordsLinked to original sources

Cryoplasty for arterial restenosis.

OBJECTIVE: A prospective follow-up study of patients with arterial restenosis undergoing cryoplasty. MATERIALS & METHODS: Between May 2004 and June 2005, 10 patients with restenosis following ilio-femoral endovascular treatment underwent twelve cryoplasty procedures. All patients had had at least one previous episode of stenosis treated by conventional endovascular methods and had suffered further restenosis. The indications for treatment were grafts at risk (n=5) and symptomatic in-stent restenosis (n=5). Two patients underwent re-cryoplasty. Cryoplasty was performed in accordance with manufacturer's instructions using 6-8mm balloons. All patients had Doppler ultrasound evaluation at 1, 3, 6 and 12 months. RESULTS: All procedures had angiographically successful immediate outcome with <30% residual stenosis. Non flow limiting dissection was evident in two cases. In six procedures (50%), restenosis was evident within 6 months post-procedure, whilst in the other six, there was progressive restenosis appearing between 6-12 months. Five cryoplasty procedures have needed endovascular re-intervention due to symptomatic high-grade restenosis and a sixth is awaiting surgery. CONCLUSION: Cryoplasty is of no value in patients with restenosis in the iliofemoral segment with half the procedures failing within six months and all of them within the first year. Evidence to support the use of cryoplasty in the peripheral arterial restenotic lesions is lacking.

Aged↗

Carbon dioxide angiography: a simple and safe system of delivery.

Carbon dioxide (CO2) is an established alternate angiographic contrast agent, which can be delivered by pump or hand injection. We describe a simple, safe and inexpensive hand injection system that delivers a known volume of CO2 at atmospheric pressure and prevents contamination with room air.

Angiography↗

Oestrogens and prostate cancer.

Androgens are essential for stimulating normal development, growth and secretory activities of the prostate whereas oestrogens are generally regarded as inhibitors of growth. Evidence for the local synthesis of oestrogens includes the detection of aromatase mRNA and protein in the stroma of human non-malignant tissues and in malignant tissue, where it is detected in epithelial tumour cells. As well, aromatase activity was measured by biochemical assay and protein was detected in prostatic non-malignant and tumour cell lines. Taken together with the identification of direct oestrogenic actions on the prostate, these results suggest that alterations in local oestrogen synthesis may have significant consequences in malignancy of these organs. Genetically modified mouse models were studied in order to evaluate the action of oestrogens alone or in combination with androgens on the prostate gland. Hypogonadal (hpg) mice are deficient in gonadotrophins and androgens but showed direct proliferative responses to oestradiol. The responses were characterised by discrete lobe-specific changes including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia. The aromatase knockout (ArKO) mouse, deficient in oestrogens due to a non-functional aromatase enzyme, developed prostatic hyperplasia during the lifelong exposure to elevated androgens, however, no malignant changes were detected in the prostate at any time. In contrast, combined androgen and oestrogen treatment has been shown to induce prostatic dysplasia and adenocarcinoma. These results demonstrate that malignant changes to the prostate gland are dependent upon both androgenic and oestrogenic responses and that neither hormone alone is sufficient to evoke aberrant patterns of growth, resulting in malignancy.

Androgens↗

Venous covered stent: successful occlusion of a symptomatic internal iliac arteriovenous fistula.

We report the placement of a covered stent within the internal iliac vein (IIV) to occlude a symptomatic iatrogenic internal iliac arteriovenous fistula following an abdominal aortic graft. Angiography revealed a direct communication between an internal iliac graft to artery anastomosis and the right IIV with rapid shunting into the inferior vena cava and a small associated pseudoaneurysm. Femoral, brachial or axillary arterial access was precluded. The fistula was successfully occluded by a stent-graft placed in the IIV. Arteriovenous fistula can be treated in a number of ways including covered stent placement on the arterial side. To the best of our knowledge this is the first time placement in a vein has been described. Where access is difficult or the procedure carries a high risk of complication, a venous covered stent may offer an alternative.

Angiography↗

The contribution of inhibins and activins to malignant prostate disease.

The normal human prostate expresses inhibin and activin subunits. In prostate cancer, the inhibin alpha subunit gene is down regulated and this is associated with loss of heterozygosity (LOH) at the gene locus and methylation of the promoter. These data support the hypothesis that the inhibin alpha subunit is tumor suppressive in the prostate. The pluripotent effects of activins and the similarities to transforming growth factor beta (TFGbeta) suggest a role for activins in progression to malignancy, whereby, the normal growth inhibitory action of activin A observed on benign cells is lost with the acquisition of activin resistance in prostate cancer cells. The mechanisms of rendering tumor cells resistant to activin A may include: alteration in activin binding protein (follistatin) synthesis and/or dimerisation with activin beta(C) to form novel activin dimers. The contribution of the activin signalling cascade to malignancy requires further evaluation to identify the synergies and differences to other members of the TGFbeta superfamily.

Activins↗

Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland.

Although androgens are the main steroids controlling the growth of the mammalian prostate, increasing evidence demonstrates that estrogens also regulate prostate development and growth. This study describes the effects of estrogen deficiency using aromatase knockout mice (ArKO) with targeted disruption of the cyp19 gene. Serum and tissue testosterone and 5alpha-dihydrotestosterone as well as serum PRL levels are significantly (P < 0.05) elevated in mature male ArKO mice. Histological, stereological, and immunohistochemical studies demonstrated enlargement of the ventral, anterior, and dorsolateral lobes of the prostate in young and older ArKO mice. Hyperplasia of the epithelial, interstitial, and luminal compartments was identified and associated with up-regulation of androgen receptors. There was no evidence of malignancy as the animals aged (up to 56 weeks). The changes observed in the prostates of ArKO mice were unaffected by maintaining mice on regular or soy-free diets. It is concluded in ArKO mice that, despite the long-term elevation of androgens and PRL, the absence of estrogen in these animals does not result in induction of malignancy in the prostate gland.

Androgens↗

Spiral CT of the abdomen: increased diagnostic potential.

Over the last 10 years, spiral CT has become the optimal method of performing all CT within the abdomen and pelvis. Not only has the technique improved the quality of individual examinations, it has also opened up many new diagnostic possibilities which are currently being evaluated and compared with the concurrent advances in ultrasound and MRI. These new diagnostic possibilities are discussed in this review article. So too are the economic advantages of the shorter data-acquisition times which also make the examination much better tolerated by the patient.

Acute Disease↗

Treatment of infrarenal aortic stenosis by stent placement: a 6-year experience.

There is a significant re-stenosis rate with percutaneous treatment of stenoses of the infrarenal abdominal aorta with balloon angioplasty. Since 1990 the authors have primarily treated local infrarenal aortic stenoses with metallic endoluminal stents. The authors' experience with 12 consecutive patients (nine women and three men, aged from 30 to 72 years (mean age = 57 years)) is presented. Follow-up is available in 11 cases over 7-78 months (mean 32 months). The procedure was technically successful in all patients. Of the 11 patients with follow-up available, claudication was cured (n = 7) or significantly improved (n = 4). Those with persisting claudication had concurrent distal arterial disease. Periprocedural complications occurred in five cases, with two significant complications. One case required iliac angioplasty for embolized aortic atherosclerotic plaque, and one case required surgical thrombectomy and vein patch for iliac thrombosis complicating iliac dissection, without long-term sequelae in either case. One patient has had recurrent symptomatic aortic stenosis occurring 6 years after initial stenting, which responded to further stent insertion. Primary patency of 91% and secondary assisted patency of 100% has been achieved. Primary treatment of infrarenal aortic stenosis with endoluminal stenting results in high patency rates, with low morbidity and relatively low complication rates.

Adult↗

Subclavian and internal jugular veins at Doppler US: abnormal cardiac pulsatility and respiratory phasicity as a predictor of complete central occlusion.

In 21 consecutive patients, the authors analyzed changes in venous Doppler waveforms of damped or diminished cardiac pulsatility and respiratory phasicity. Each patient was suspected of having upper limb venous thrombosis, but thrombus was not visible at gray-scale ultrasonography (US) in the subclavian and brachiocephalic veins. US findings were compared with phlebographic findings. The results show that US can be used to establish the presence or absence of thrombosis in the distal portion of the brachiocephalic or subclavian veins, which are inaccessible to direct insonation.

Adult↗

Expression of activin A and follistatin core proteins by human prostate tumor cell lines.

Activin and follistatin (FS) messenger RNA and protein are expressed and localized to human prostate tissue from men with high grade cancer and to human prostate tumor cell lines LNCaP, DU145, and PC3. Although activin A induces apoptosis and inhibits cell proliferation in LNCaP cells, PC3 cells are insensitive to the effect of exogenous addition of activin A. The results of this study show that activin A and FS are produced and can be measured by specific enzyme-linked immunosorbent assays in PC3 cells and media but are not detectable in LNCaP cells. Over 10 days in culture, the production of activin A by PC3 cells declines and is inversely correlated (r = -0.779) to FS288 production, which steadily increases and is significantly elevated compared with Day 1 of culture. The presence of FS288 and FS315 proteins was confirmed by immunocytochemistry and showed that only PC3 cells produced the FS288 isoform. Western blotting of PC3 cell media confirmed the presence of the FS288 isoform. Blockade of FS288 activity with a neutralizing antibody rendered PC3 cells responsive to activin A, as measured by inhibition of proliferation. Collectively, these results suggest that PC3 tumor cells are insensitive to activin A because they produce measurable amounts of activin ligand and FS288 protein, which is capable of blocking the autocrine response of these cells to activin A.

Activins↗

Percutaneous transjejunal biliary intervention: 10-year experience with access via Roux-en-Y loops.

PURPOSE: To assess the safety and efficacy of percutaneous retrograde transjejunal cholangiography and biliary intervention for benign and malignant disease. MATERIALS AND METHODS: The clinical and radiographic records of 43 patients (31 with benign and 12 with malignant disease) who had undergone percutaneous retrograde transjejunal biliary intervention over a 10-year period at a single institution were reviewed. One hundred eighty-one procedures were performed via a fixed Roux-en-Y loop and 15 via an unfixed loop. RESULTS: Percutaneous retrograde transjejunal cholangiography was attempted on 196 occasions (143 for benign and 53 for malignant disease). Primary successful access was obtained in 181 (92.3%). Adjunctive percutaneous transhepatic cholangiography improved successful access in an additional seven procedures, to 188 (95.9%). Interventions included stricture dilation, stone extraction, stent insertion, and brachytherapy. The mean number of biliary interventions and the mean interval between them were 3.1 interventions and 5.9 months in the benign group and 3.6 interventions and 3.8 months in the malignant group. The complication rate was 4.1%, with no deaths or episodes of biliary sepsis. CONCLUSION: Percutaneous transjejunal biliary access allows repeated interventions over many years with a low morbidity. Routine superficial fixation of Roux-en-Y loops is recommended for all biliary-enteric anastomoses to allow use of this safe and effective approach for any subsequent biliary intervention.

Anastomosis, Roux-en-Y↗

Growth inhibitory response to activin A and B by human prostate tumour cell lines, LNCaP and DU145.

Activins are growth and differentiation factors which have been shown to have proliferative and antiproliferative actions in many tissues. In addition, they have been implicated in tumourigenesis in reproductive tissues. Although activin and inhibin are present in rat ventral prostate, inhibin beta, but not alpha, subunit proteins have been detected in the human prostate epithelial tumour cell lines LNCaP, DU145 and PC3. With this absence of capacity to produce inhibins, the aims of this study were to determine the effect of activin A and B and follistatin on DNA synthesis by these human prostate tumour cell lines. The results demonstrate a differential response to exogenously added activin A and B on DNA synthesis in vitro by the tumour cell lines. The inhibitory effects were observed on LNCaP cells in the absence or presence of stimulation with 1 nM 5 alpha-dihydrotestosterone and on the androgen-independent DU145 cells, but not the PC3 cells. Activin A caused a dose-dependent inhibition of DNA synthesis and proliferation by LNCaP and androgen-independent DU145 cells which was maximal at 8 ng/ml. The effect of exogenously added activin A was completely reversed by follistatin, but not by inhibin A. The addition of human recombinant FS 288 alone (400 ng/ml) did not have any effect on DNA synthesis, whereas inhibin A alone (400 ng/ml) caused a significant inhibition of DNA synthesis. The capacity of all three cell lines to produce activins and follistatins was demonstrated by the expression of the mRNAs and confirmed by the localisation of immunoreactivity for these ligands to the cytoplasm of the tumour cells. The growth inhibitory response to activins A and B by LNCaP and DU145 cells, and the ability of follistatin to block these effects, suggest that the autocrine interactions between activins and follistatins have a role in the regulation of LNCaP and DU145 prostate tumour cell growth.

Activins↗

Application of a chromogenic bioassay procedure for the measurement of the proliferation of endothelial cells in vitro under the influence of the effects of steroid hormones and growth factors.

Development of in vitro procedures which permit the measurement of the synergistic biological influences of polypeptide growth factors and steroid hormones on cellular processes represents an important objective in reaching an understanding of the molecular basis of many physiological events, including those associated with the proliferation of endothelial cells and the subsequent angiogenesis which occurs, for example, during the estrous cycle and wound repair. The present investigations were undertaken to examine the use of nonradioisotopic procedures for the bioassay of polypeptide growth factors, such as basic fibroblast growth factor (bFGF), known to exert effects on the proliferation and migration of endothelial cells, and to overcome some of the recognised sensitivity limitations with endothelial cell proliferation assays based on the [3H]thymidine uptake methods due to the cell passage number and culture conditions. The experimental results confirm these objectives with establishment of a simplified chromogenic procedure for the sensitive determination of the effects of the steroid hormones, estradiol and progesterone, on the proliferation of endothelial cells in culture, either directly or via mediation of the effects of bFGF at low concentration levels. This procedure has provided experimental data suggesting that a hitherto unrecognised synergy may exist between these steroids and bFGF, with both estradiol and progesterone significantly antagonising the bFGF-stimulated proliferative response with bovine aortic endothelial cells (BAEC) in culture. Progesterone alone was also capable of directly stimulating BAEC proliferation, albeit transiently. Neither estradiol or progesterone affected the proliferation of the control 3T3 fibroblast cell population, in the presence or absence of a stimulatory dose of bFGF.

3T3 Cells↗

Transient splenic inhomogeneity with contrast-enhanced CT: mechanism and effect of liver disease.

PURPOSE: To use computed tomography (CT) and functional imaging to characterize the physiologic processes that result in transient splenic inhomogeneity during contrast material enhancement and determine their value in detection of diffuse liver disease. MATERIALS AND METHODS: CT scan data from nine control patients and 13 patients with diffuse liver disease were used to create functional images that displayed splenic perfusion and time to peak enhancement. A pixel-by-pixel analysis was used to create these images. RESULTS: Areas of early enhancement demonstrated higher perfusion and vice versa. In patients with liver disease, splenic perfusion values fell from 1.44 to 1.22 mL/min/mL in the areas that showed early enhancement and 1.24 to 0.89 mL/min/mL in the areas that showed late enhancement. As splenic perfusion values fell, the size of the regions that showed late enhancement increased. CONCLUSION: The combination of functional images and CT data has clarified the mechanism by which transient splenic inhomogeneity occurs and is of potential value in the detection of diffuse liver disease.

Adult↗

Acute toxic inhalations.

Many inhaled toxins are capable of producing illness; either through direct pulmonary damage or by their systemic toxicity. Occupational exposures and fires are the most common sources of the numerous agents accountable for accidental inhalational injuries. When obvious historical evidence or a heightened suspicion for an acute inhalational exposure does not exist, misdiagnosis and maltreatment are likely to occur. When properly identified, recovery is likely if expedient decontamination and supportive care are provided to the victim. Preventing hypoxemia is central to the treatment of all pulmonary and systemic inhalational injuries but some cases, such as those involving organophosphate poisonings and chemical asphyxiation, antidotes are frequently critical to a patient's recovery.

Acute Disease↗

Endovascular embolization of visceral artery aneurysms with ethylene-vinyl alcohol (Onyx): a case series.

We report the application of the liquid embolic agent ethylene-vinyl alcohol (Onyx; MicroTherapeutics, Irvine, CA, USA) in the management of visceral artery aneurysms. The technique and indications for using Onyx are discussed with emphasis on the management of wide-necked aneurysms and maintenance of patency of the parent vessel. None of the cases was considered suitable for stent-grafting or embolization with conventional agents. Two aneurysms of the renal artery bifurcation and one aneurysm of the inferior pancreaticoduodenal artery were treated. Following treatment there was complete exclusion of all aneurysms. There was no evidence of end-organ infarction. Follow-up with intervals up to 6 months has shown sustained aneurysm exclusion. Onyx is known to be effective in the management of intracranial aneurysms. Our experience demonstrates the efficacy and applicability of the use of Onyx in the treatment of complex visceral artery aneurysms.

Aged↗