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Biomedical subjects

T Hartshorne

Publications and source records attributed to T Hartshorne.

At least 19 recordsLinked to original sources

Role of superficial venous surgery in patients with combined superficial and segmental deep venous reflux.

OBJECTIVES: superficial venous surgery heals chronic venous ulceration (CVU) in the majority of patients with isolated superficial venous reflux (SVR). This study examines the role of superficial venous surgery in patients with combined SVR and segmental deep venous reflux (DVR). METHODS: combined SVR and segmental DVR was diagnosed by venous duplex in 53 limbs in 49 patients (24 men and 25 women of median age 66, range 27-90, years). Fourteen limbs had varicose veins (CEAP class 2-4) and 39 (74%) had active CVU (CEAP class 6). Duplex ultrasound was performed before and three months after local anaesthetic superficial venous surgery. Perforator vein surgery, skin grafting and compression bandaging or hosiery were not used. RESULTS: forty-two limbs with long saphenous vein (LSV) reflux underwent sapheno-femoral disconnection, 10 with short saphenous vein (SSV) reflux underwent sapheno-popliteal disconnection and one limb with LSV and SSV reflux had sapheno-femoral and sapheno-popliteal disconnection. Segmental DVR was confined to the superficial femoral vein (SFV) in 16 limbs, below knee popliteal vein (BKPV) in 25 and gastrocnemius vein (GV) in 12 limbs. Overall, duplex demonstrated post-operative resolution of segmental DVR in 26 of 53 (49%) limbs. Resolution of segmental SFV reflux occurred in 12 of 16 (75%) limbs compared with 14 of 37 (38%) limbs with segmental BKPV or GV reflux (p=0.018). Segmental DVR resolved in 19 of 39 (49%) limbs with CVU and ulcer healing occurred in 30 of 39 (77%) limbs at 12 months with a median time to healing of 61 (range 14-352) days. Segmental DVR resolved in 14 of 30 (47%) limbs with a healed ulcer: 7 of 9 (78%) limbs with SFV and 7 of 21 (33%) with BKPV or GV reflux (p=0.046). CONCLUSIONS: these data demonstrate that in patients with combined SVR and segmental DVR, superficial venous surgery alone corrects DVR in almost 50% of limbs and is associated with ulcer healing in 77% of limbs at 12 months. These findings suggest an extended role for superficial venous surgery in the management of patients with complicated venous disease.

Adult↗

The diagnosis and management of 689 chronic leg ulcers in a single-visit assessment clinic.

OBJECTIVES: accurate diagnosis is essential if patients with chronic leg ulceration are to receive optimal treatment. This prospective study describes the findings of a standardised assessment protocol and the initial management of a consecutive series of patients with chronic leg ulceration presenting to a single-visit leg ulcer assessment clinic. METHODS: between January 1993 and January 1999, a total of 555 patients (220 men and 335 women of median age 73, range 28-95 years) with 689 chronic leg ulcers were assessed. Full clinical assessment, ankle:brachial pressure index and lower limb venous duplex scan were performed according to a standardised protocol and diagnostic and management data were recorded prospectively on a computerised database. RESULTS: venous disease alone was responsible for 496 of 689 (72%) ulcers. Isolated superficial venous reflux (SVR) was identified in 52% of limbs and two-thirds of these had superficial venous surgery. Combined SVR and segmental deep venous reflux (DVR) was present in 13%, and full-length DVR was present in 33% of limbs. Nineteen (4%) limbs had deep venous stenosis or obstruction. Overall, superficial venous surgery was performed in 43% and compression bandages or hosiery alone were applied in 52% of limbs. Mixed arterio-venous ulceration was present in 100 (14.5%) limbs of which 56 had arterial revascularisation, 38 had superficial venous surgery and 23 had compression alone. Fifteen limbs with pure arterial ulceration had angioplasty (n=13) or simple dressings alone (n=2). Ulceration due to lymphoedema (n=17), mixed lymphoedema and venous reflux (n=11) and other causes (n=50) were managed by compression, dressings or skin grafting. CONCLUSIONS: a standardised protocol of clinical and duplex assessment can lead to a diagnosis in 97% of chronic leg ulcers. Duplex is essential to confirm or exclude potentially correctable venous disease and allow tailored surgical intervention for those patients who many benefit.

Adult↗

Trypanosoma brucei 5'ETS A'-cleavage is directed by 3'-adjacent sequences, but not two U3 snoRNA-binding elements, which are all required for subsequent pre-small subunit rRNA processing events.

Trypanosoma brucei pre-rRNA processing commences by cleavage near the 5' end of 5.8 S sequences. The 5' external transcribed spacer (5'ETS) is removed from pre-small subunit (SSU) rRNAs by sequential cleavages at internal A' and A0 sites, and A1 at the 5' end of SSU rRNA. The A' and A0 sites positionally resemble the U3 small nucleolar RNA-dependent, primary pre-rRNA cleavages of vertebrates and yeast, respectively. Uniquely in T. brucei, two U3-crosslinkable 5'ETS sites are essential for SSU rRNA production: site1b is novel in its 3' location to the A' site, and site3 lies upstream of A0 in a position analogous to the yeast U3-binding site. Here, in vivo analysis of mutated 5'ETS sequences shows that sequences 5' to the A' site are not needed for A' cleavage or SSU rRNA production. A' cleavage is linked to, but is not sufficient to trigger, downstream pre-SSU rRNA processing events. These events require an intact 11 nt sequence, 3'-adjacent to A', which directs efficient and accurate A' cleavage. Neither the A' nearby site1b nor the site3 U3-binding elements affect A' processing, yet each is required for A0 and A1 cleavage, and SSU rRNA production. The same U3 3' hinge bases evidently bind a core element, UGUu/gGGU, within site1a and site3; the U3-site1b interaction is less reliant on base-pairing than the U3-site3 interaction. As yeast U3 5' hinge bases pair to 5'ETS sequences, it is clear that distinct U3 hinge regions can interact at both novel and related 5'ETS sites to promote 3'-proximal 5'ETS processing events in diverse organisms. The T. brucei data fit a model wherein processing factors assemble at the 5'ETS site1a to affect A' cleavage and stabilize a U3-site1b complex, which may work in concert with the downstream U3-site3 complex to assist processing events leading to ribosomal SSU production.

Animals↗

The clinical management and outcome of venous ulcers in legs with deep-venous obstruction.

OBJECTIVE: as a result of a serious complication from compression bandaging in a patient with venous ulceration and deep-vein obstruction, a policy of incremental compression in such limbs has been developed. The purpose of this retrospective study is to review the outcome of this policy. DESIGN: limbs with deep-venous obstruction (stenosis or occlusion) were treated initially with 3-layer compression bandaging and reviewed 24 h later. If 3-layer bandaging was tolerated, it was re-applied for a further 48 h. If there were no problems, then 4-layer bandaging was applied and the patient reviewed at 24 and 72 h. If 4-layer bandaging could not be tolerated, the limb was returned to 3-layer bandaging. RESULTS: of 325 limbs seen in a venous-ulcer clinic, 22 (7%) had deep-vein obstruction. Fifteen (68%) limbs were able to tolerate 4-layer bandaging, five (23%) could tolerate 3-layer bandaging and two limbs (9%) could only tolerate class 2 compression hosiery. The overall 1-year healing rate was 55%. There were no serious complications from bandaging. CONCLUSIONS: a protocol of incremental compression bandaging is safe in ulcerated legs with deep-vein obstruction and produces healing in up to 55% of cases.

Aged↗

Characterization of an essential RNA secondary structure in the 3' untranslated region of the murine coronavirus genome.

We have previously identified a functionally essential bulged stem-loop in the 3' untranslated region of the positive-stranded RNA genome of mouse hepatitis virus. This 68-nucleotide structure is composed of six stem segments interrupted by five bulges, and its structure, but not its primary sequence, is entirely conserved in the related bovine coronavirus. The functional importance of individual stem segments of this stem-loop was characterized by genetic analysis using targeted RNA recombination. We also examined the effects of stem segment mutations on the replication of mouse hepatitis virus defective interfering RNAs. These studies were complemented by enzymatic and chemical probing of the stem-loop. Taken together, our results confirmed most of the previously proposed structure, but they revealed that the terminal loop and an internal loop are larger than originally thought. Three of the stem segments were found to be essential for viral replication. Further, our results suggest that the stem segment at the base of the stem-loop is an alternative base-pairing structure for part of a downstream, and partially overlapping, RNA pseudoknot that has recently been shown to be necessary for bovine coronavirus replication.

3' Untranslated Regions↗

Two 5'-ETS regions implicated in interactions with U3 snoRNA are required for small subunit rRNA maturation in Trypanosoma brucei.

Early pre-rRNA processing events were examined in the ancient protozoan parasite Trypanosoma brucei and found to have both distinctive and conserved features. Two 5'-ETS cleavages occur: A' and the newly discovered A0. A' and A0 appear related to vertebrate and yeast primary pre-RNA cleavage sites, respectively. However, trypanosomatid primary rRNA transcripts can first be processed at the ITS1/5.8S boundary and 5'-ETS sequences then removed by consecutive cleavages at A', A0 and A1 at the 5'-ETS/SSU rRNA junction. 5'-ETS sequences previously crosslinked to U3 snoRNA were tested for their roles in rRNA processing using our new tagged rRNA system. Two distinct A'-adjacent sequence elements, which may pair with U3 hinge bases, were specifically required for SSU rRNA production, as was a downstream element. The latter element appears conserved with the yeast 5'-ETS U3 binding sequence, required for A0, A1 and A2 cleavages, in that they both share 10 bases complementary with U3 hinge sequences and lie upstream from A0 and A1 sites located in a potential stem-loop structure. The distinctive positioning of putative trypanosomatid U3 binding sites with respect to A" and A0 cleavages suggests that different U3-dependent mechanisms may direct each processing event.

Animals↗

Colour-coded duplex imaging and dependent Doppler ultrasonography in the assessment of cruropedal vessels.

BACKGROUND: It has been suggested that ultrasonography could replace diagnostic arteriography in the assessment of patients who present with leg ischaemia. This study investigated a group of consecutive patients who had femorodistal bypass and who were assessed before operation with colour-coded duplex and dependent Doppler insonation alone. METHODS: Thirty-seven consecutive patients with critical lower limb ischaemia underwent surgical exploration with a view to femorodistal bypass. Results of preoperative colour-coded duplex and dependent Doppler insonation were compared with intraoperative arteriograms and surgical findings. RESULTS: There was very good agreement between colour-coded duplex imaging and dependent Doppler insonation with intraoperative angiography and surgical findings in the prediction of the optimal run-off vessel (kappa = 1.0) and the site of the distal anastomosis (kappa = 0.85; 95 per cent confidence interval 0.71-1.0). There was also very good agreement between dependent Doppler insonation and intraoperative arteriography (kappa = 1.0) in predicting pedal arch patency and the predominant feeding vessel. CONCLUSION: Assessment of leg arteries before femorodistal bypass can be performed accurately with non-invasive colour-coded duplex imaging and dependent Doppler insonation alone, thus obviating the need for preoperative arteriography.

Adult↗

Role of superficial venous surgery in the treatment of venous ulceration.

BACKGROUND: The aim of this study was to determine the ability of superficial venous surgery to heal venous ulcers in lower legs with isolated superficial venous incompetence. METHODS: This was a prospective study of patients recruited from a venous ulcer assessment clinic. Ulcers were considered venous if the ankle : brachial pressure index was greater than 0.8 and duplex imaging showed venous reflux. Patients with isolated superficial venous incompetence were offered saphenofemoral and/or saphenopopliteal surgery. Neither perforator surgery, skin grafting nor postoperative compression hosiery or bandaging was used. RESULTS: A total of 122 legs with normal deep veins underwent superficial venous surgery. Ninety procedures (74 per cent) were done under local and 32 (26 per cent) under general anaesthesia. Sixty operations (49 per cent) were done as a day case. The median time to healing was 18 (95 per cent confidence interval 14-21) weeks and the cumulative 6-, 12- and 18-month healing rates were 57, 74 and 82 per cent respectively. CONCLUSION: In patients with venous ulceration and isolated superficial venous incompetence, superficial venous surgery can produce ulcer healing in the majority of patients without the need for perforator surgery, postoperative compression bandaging or skin grafting.

Adult↗

Use of colour duplex imaging to diagnose and guide angioplasty of lower limb arterial lesions.

BACKGROUND: The purpose of this study was to investigate whether colour duplex imaging alone could safely and effectively be used to diagnose lower limb arterial lesions and guide subsequent percutaneous transluminal angioplasty (PTA). METHODS: Patients with discrete lower limb arterial lesions, preferably stenoses, which could be visualized clearly by colour duplex imaging were selected for duplex-guided PTA. Duplex-guided PTA was performed in an operating theatre using conventional balloon catheters. RESULTS: Duplex imaging was used to diagnose and guide PTA of 55 arterial lesions in 50 legs of 45 patients. There were 53 stenoses and two occlusions. The median (range) ankle : brachial pressure index was 0. 86 (0.52-1.10) before dilatation and 1.00 (0.83-1.40) immediately after dilatation (P = 0.0001). There were no complications during or after any of the procedures and 46 of the 47 symptomatic legs were markedly improved at a median follow-up of 23 days. Radiographic imaging was not required for any of the procedures. CONCLUSION: It is possible to diagnose and angioplasty lower limb arterial lesions using colour duplex imaging alone.

Angioplasty, Balloon↗

Venous ulceration and continuous flow in the long saphenous vein.

OBJECTIVE: To determine the clinical significance of continuous flow in the long saphenous vein in limbs with venous ulceration. DESIGN: Retrospective review. PATIENTS AND METHODS: Review of 1608 consecutive limbs undergoing colour duplex scanning for venous disease over a 43 month period. RESULTS: Continuous flow in the long saphenous vein is seen in 8% of limbs with venous ulceration and in 37% of limbs with deep venous obstruction. Sixty-six per cent of ulcerated limbs with continuous flow in the long saphenous vein had deep venous obstruction, 27% had deep venous reflux with cellulitis and 7% had lymphoedema in addition to venous ulceration. CONCLUSION: Continuous flow in the long saphenous vein in patients with venous ulceration should alert the clinician to the possibility of deep venous obstruction. Such limbs should be treated by compression bandaging with extreme caution.

Blood Flow Velocity↗

Distinct regions of U3 snoRNA interact at two sites within the 5' external transcribed spacer of pre-rRNAs in Trypanosoma brucei cells.

U3 snoRNA is required for early pre-rRNA processing events that include cleavage of the 5' external transcribed spacer (5'ETS) and 18S rRNA maturation. Herein, psoralen RNA crosslinking has been used to indicate novel in vivo interactions between the minimally-sized Trypanosoma brucei U3 snoRNA and pre-rRNAs. Two discrete U3 crosslinks were mapped to 5'ETS sequences, then individually isolated by hybrid selection following digestion of pre-rRNAs. Crosslink positions within these U3-site1 and U3-site2 complexes were resolved by RNaseH digestion and primer extension analyses. Hinge bases of U3 contacted site1 bases U140 and U142 just 3' of the processed primary site. This is the first experimental evidence of a U3 RNA interaction adjacent to a major 5'ETS cleavage site and supports a critical role for U3 in its processing. Highly conserved box A bases contacted site2 base U945, 187 nt upstream of 18S-like rRNA sequences. Site2 sequences are not required for primary processing, thus, a U3 interaction here might have roles in subsequent downstream processing events. These results clearly demonstrated that distinct U3 snoRNA sequences crosslinked different regions of the 5'ETS and support a model for U3 as a multifunctional snoRNA.

Animals↗

A clinical and haemodynamic investigation into the role of calf perforating vein surgery in patients with venous ulceration and deep venous incompetence.

OBJECTIVE: To determine the clinical efficacy and local haemodynamic effects of perforating vein surgery in ulcerated limbs with combined deep and perforating vein incompetence. DESIGN: Prospective, interventional study. MATERIALS AND METHODS: Seven ulcerated limbs with combined primary deep and perforating vein incompetence were studied. Clinical efficacy was determined by ultimate ulcer healing and reduction in ulcer area, local haemodynamics were assessed at three sites with photoplethysmographic 90% venous refilling times (PPG RT90); both assessments were performed pre- and 1-month postoperatively. RESULTS: None of the ulcers healed following perforating vein surgery, the median (range) ulcer areas pre- and postoperatively were 31 (7-685) cm2 and 35.5 (7-796) cm2 (Wilcoxon p = 0.07). Preoperative PPG RT90 demonstrated a global abnormality of venous function at all sites examined that persisted after perforating vein surgery. CONCLUSION: In the presence of deep venous incompetence perforating vein surgery had no influence on venous function or ulcer healing. We conclude that perforating vein surgery is not indicated for the treatment of venous ulceration in limbs with primary deep venous incompetence.

Aged↗

Carotid endarterectomy without angiography does not compromise operative outcome.

OBJECTIVES: Carotid angiography is associated with a 2% risk of stroke and, since the advent of colour-duplex ultrasound, its role in the assessment of patients with carotid disease has been the subject of debate. The aim of this study was to evaluate a policy of adopting routine duplex supplemented by selective angiography on operative outcome over a 5-year period. METHODS: A prospective audit of the results of carotid endarterectomy without routine angiography from January 1992 to December 1996. Angiography was performed only if the ultrasonography was concerned about the distal or proximal extent of disease or to assess subocclusion. RESULTS: During the study period, 494 carotid endarterectomies were performed but only 35 patients underwent carotid angiography. The indications for angiography were subocclusion/string sign in 22 patients, to assess the limits of proximal or distal disease in 12 and abnormal anatomy in one. During the 5-year study period the overall perioperative death and/or stroke rate was 4.2%. By 1997, the perioperative stroke rate had fallen to 1.3%. In no case in this series was the operation abandoned due to unexpected findings. CONCLUSION: Although concerns exist about the precise duplex criteria for diagnosing a severe stenosis, this study has shown that a policy of selective angiography does not compromise patient safety or operability and avoids the unnecessary mortality, morbidity and costs associated with routine angiography.

Angiography↗

Role of saphenous vein surgery in the treatment of venous ulceration.

BACKGROUND: This paper describes local anaesthetic saphenous disconnection in elderly patients for the treatment of venous ulceration in legs with either saphenous venous reflux alone or in combination with deep venous reflux. METHODS: Ambulatory venous pressure was measured in 16 legs with saphenous vein reflux alone and in nine legs with combined deep and saphenous venous reflux before, immediately after and 3 months after saphenofemoral or popliteal disconnection. Ulcer area was measured by computerized planimetry before surgery and at 1 and 3 months after operation. No compression bandages or hose were applied after surgery unless the ulcers had not begun to heal after 1 month. RESULTS: In legs with saphenous reflux alone all ulcers healed without compression bandages at a median of 81 (range 14-253) days and the pressure relief index (PRI) improved significantly both after surgery and at follow-up. None of the ulcers in the nine limbs with saphenous and deep venous reflux healed without compression bandaging and the PRI was unchanged immediately following surgery and at follow-up. CONCLUSION: Saphenous vein disconnection improves venous function and heals venous ulcers without compression bandaging if the deep veins are normal. This procedure under local anaesthetic may be particularly suitable for elderly patients, but long saphenous vein stripping should be added in young patients.

Aged↗

Role of magnetic resonance angiography for assessment of abdominal aortic aneurysm before endoluminal repair.

BACKGROUND: A detailed knowledge of the morphology of the aorta and iliac arteries is an important prerequisite for successful endoluminal abdominal aortic aneurysm (AAA) repair. The best method of preoperative evaluation remains to be determined. METHODS: A prospective study was undertaken between January 1994 and July 1995 to assess the ability of computed tomography (CT), magnetic resonance angiography (MRA), colour duplex imaging and intra-arterial digital subtraction angiography (IA-DSA) to visualize AAA morphology. RESULTS: Eighty-two consecutive patients (64 men, 18 women) with AAA were assessed with MRA, contrast-enhanced CT, colour duplex imaging and IA-DSA. Median age was 74 (range 59-87) years and median AAA diameter was 5.7 (range 3.5-9.7) cm. Five patients were unable to tolerate CT or MRA examination. Seventy-seven patients underwent both CT and MRA. Of these, 55 also had a colour duplex scan and 32 underwent arteriography. The scans were assessed by an independent blinded observer. MRA was significantly better (P < 0.01) at visualizing AAA morphology compared with CT and colour duplex imaging. There was no statistically significant difference between MRA and arteriography. CONCLUSION: MRA is useful in patient selection for endoluminal AAA repair, as it avoids use of iodinated contrast medium and ionizing radiation.

Aged↗

Three small nucleolar RNAs identified from the spliced leader-associated RNA locus in kinetoplastid protozoans.

First characterized in Trypanosoma brucei, the spliced leader-associated (SLA) RNA gene locus has now been isolated from the kinetoplastids Leishmania tarentolae and Trypanosoma cruzi. In addition to the T. brucei SLA RNA, both L. tarentolae and T. cruzi SLA RNA repeat units also yield RNAs of 75 or 76 nucleotides (nt), 92 or 94 nt, and approximately 450 or approximately 350 nt, respectively, each with significant sequence identity to transcripts previously described from the T. brucei SLA RNA locus. Cell fractionation studies localize the three additional RNAs to the nucleolus; the presence of box C/D-like elements in two of the transcripts suggests that they are members of a class of small nucleolar RNAs (snoRNAs) that guide modification and cleavage of rRNAs. Candidate rRNA-snoRNA interactions can be found for one domain in each of the C/D element-containing RNAs. The putative target site for the 75/76-nt RNA is a highly conserved portion of the small subunit rRNA that contains 2'-O-ribose methylation at a conserved position (Gm1830) in L. tarentolae and in vertebrates. The 92/94-nt RNA has the potential to form base pairs near a conserved methylation site in the large subunit rRNA, which corresponds to position Gm4141 of small rRNA 2 in T. brucei. These data suggest that trypanosomatids do not obey the general 5-bp rule for snoRNA-mediated methylation.

Animals↗

Subintimal angioplasty of infrapopliteal occlusions in critically ischaemic limbs.

OBJECTIVE: To review the outcome of subintimal angioplasty of infrapopliteal artery occlusions in critically ischaemic limbs. DESIGN: Retrospective review. MATERIALS: Twenty-eight consecutive limbs with critical ischaemia that had undergone subintimal angioplasty of infrapopliteal occlusions. RESULTS: There were 32 infrapopliteal artery occlusions in 28 critically ischaemic limbs in 27 patients. The median (range) patient age was 81 (48-88) years. Seventeen limbs (61%) were ulcerated, seven (25%) were gangrenous and four (14%) had rest pain only. Twenty-five (89%) procedures were to a single calf vessel, and three (11%) procedures were to multiple calf vessels. The median (range) length of the occlusions was 7 (2-30) cm. The initial technical success rate was 27/32 (84%). There were three minor complications--one groin haematoma, one vessel perforation and one distal embolus. There were no limbs lost as a result of the procedure itself and the 30-day mortality was zero. The 12-month actuarial haemodynamic and symptomatic patencies (including initial failures) were 53% and 56%, respectively. The 12-month limb salvage rate was 85% and patient survival was 81%. CONCLUSION: We conclude that subintimal angioplasty in patients with infrapopliteal artery occlusions and critical ischaemia is safe, effective, and offers a low-risk alternative to distal reconstructive surgery.

Aged↗

Single-visit venous ulcer assessment clinic: the first year.

BACKGROUND: Venous ulceration is a significant clinical problem to both clinicians and patients. To optimize the management of patients with ulcers a single-visit, dedicated venous ulcer assessment clinic was set up. METHODS: All patients referred to the clinic during the first year were recorded prospectively. Each patient was assessed clinically and with colour-coded venous and, where indicated, arterial duplex scanning. Ulcers were classified as venous, arterial, mixed or non-vascular on a basis of ankle:brachial pressure indices and venous duplex scanning. RESULTS: Eighty-eight patients (104 limbs with ulcers) were assessed. Seventy-nine per cent of ulcers were venous, 2 per cent arterial, 12 per cent mixed and 7 per cent non-vascular. Of the 95 limbs with demonstrable venous reflux, reflux was confined to the superficial system in 57 per cent, the deep system in 6 per cent and was combined in 37 per cent of limbs. Of the 22 patients who reported previous deep vein thrombosis, nine had normal deep vein function. Some 38 per cent of limbs with no history of previous thrombosis had abnormal deep vein function. CONCLUSION: In this clinic 14 per cent of leg ulcers had a significant arterial component and over half of venous ulcers may benefit from superficial venous surgery. In many ulcerated limbs, clinical assessment alone is inadequate to detect superficial reflux or previous deep vein thrombosis.

Adult↗