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Biomedical subjects

J May

Publications and source records attributed to J May.

At least 37 records · Page 2Linked to original sources

CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation.

The CD45 transmembrane glycoprotein has been shown to be a protein phosphotyrosine phosphatase and to be important in signal transduction in T and B lymphocytes. We have employed gene targeting to create a strain of transgenic mice that completely lacks expression of all isoforms of CD45. The spleens from CD45-null mice contain approximately twice the number of B cells and one fifth the number of T cells found in normal controls. The increase in B cell numbers is due to the specific expansion of two B cell subpopulations that express high levels of immunoglobulin (IgM) staining. T cell development is significantly inhibited in CD45-null animals at two distinct stages. The efficiency of the development of CD4-CD8- thymocytes into CD4+ CD8+ thymocytes is reduced by twofold, subsequently the frequency of successful maturation of the double positive population into mature, single positive thymocytes is reduced by a further four- to fivefold. In addition, we demonstrate that CD45-null thymocytes are severely impaired in their apoptotic response to cross-linking signals via T cell receptor (TCR) in fetal thymic organ culture. In contrast, apoptosis can be induced normally in CD45-null thymocytes by non-TCR-mediated signals. Since both positive and negative selection require signals through the TCR complex, these findings suggest that CD45 is an important regulator of signal transduction via the TCR complex at multiple stages of T cell development. CD45 is absolutely required for the transmission of mitogenic signals via IgM and IgD. By contrast, CD45-null B cells proliferate as well as wild-type cells to CD40-mediated signals. The proliferation of B cells in response to CD38 cross-linking is significantly reduced but not abolished by the CD45-null mutation. We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells.

ADP-ribosyl Cyclase

Prospective study of the aetiology of infusion phlebitis and line failure during peripheral parenteral nutrition.

Four techniques of administering peripheral parenteral nutrition (PPN) were examined prospectively to investigate the role of mechanical trauma in the development of infusion phlebitis. Patients in group 1 (n = 15) were fed via a standard 18-G Teflon cannula which was removed on completion of the infusion and was rotated to the contralateral arm every day. Group 2 patients (n = 15) had a similar catheter sited in each forearm simultaneously, with rotation of the side of infusion each day. Patients in group 3 (n = 17) had a 15-cm Silastic rubber catheter inserted into a forearm vein and a standard cannula sited in the contralateral forearm, with alternation of infusion each day. Those in group 4 (n = 13) had a fine-bore 23-G silicone catheter sited in one arm only. Patients in groups 1, 2 and 3 were fed over 12-h cycles and those in group 4 for a 24-h continuous cycle. A total of 408 patient-days of PPN were given. Mean duration of PPN in groups 1-4 was 7.5, 9, 5.5 and 5 days respectively. Infusion phlebitis was not recorded in patients who had a daily change of cannula (group 1), but occurred in four patients in group 2, eight in group 3 and eight in group 4. Phlebitis scores were 0, 9, 15 and 12 for groups 1-4 respectively. Severe phlebitis and line occlusion occurred more frequently in patients with a 15-cm catheter (group 3) and in those fed continuously over 24 h (group 4). These results suggest that mechanical trauma is an important factor in the aetiology of infusion phlebitis. This can be minimized by reducing the time for which the vein wall is exposed to nutrient infusion and by reducing the amount of prosthetic material within the vein.

Adult

Results of endoluminal grafting of abdominal aortic aneurysms are dependent on aneurysm morphology.

The aim of this prospective study was to analyze the outcome of elective endoluminal grafting in patients with various morphologies of abdominal aortic aneurysms (AAA). Between May 1992 and May 1994, endoluminal repair of AAA was undertaken in 40 patients. After detailed imaging by means of CT scanning and arteriography, aneurysms were classified into one of two types according to the following criteria: type I (suitable for transfemoral implantation of a straight tube graft), AAA with a proximal neck (2 cm or longer), a distal neck (1.5 cm or longer), and an iliac artery diameter of 8 mm or greater (N = 19); or type II (requiring tapered aortoiliac or bifurcated grafts or access through an iliac approach), AAA that did not fit the type I criteria (N = 21). Radiographic guidance was used to pass the aortic endografts (38 Dacron and 2 PTFE) via a delivery sheath introduced through the femoral or iliac arteries into the aorta. The configuration of the aortic endografts was tubular in 26 patients, tapered aortoiliac in 11, and bifurcated in three. Successful endoluminal repair was achieved in 17 (89%) of 19 patients with type I AAA and in 15 (71%) of 21 patients with type II AAA. All failed endoluminal repairs proceeded to successful open repair, and there were no deaths during the period of hospitalization for the operation. The mean operative time and mean hospital stay were shorter in patients with type I AAA compared to patients with type II AAA. The incidence of postoperative complications was 37% in type I endoluminal repairs compared to 71% in type II endoluminal repairs. There was one cardiac death (procedure related) within 30 days, and there were three late deaths (one cardiac, one from liver failure in a type II AAA repair, and one from a ruptured esophagus in a type I repair). These preliminary results suggest that there is a better outcome in transfemoral endoluminal tube graft repair of aneurysms conforming to type I criteria compared to endoluminal repair of the more complex type II AAA.

Aged

Immunogenicity of full length and truncated forms of the human immunodeficiency virus type I envelope glycoprotein.

We have monitored the immunogenicity of a V1V2 sub-fragment of gp 120 in contrast to the full length protein and to a truncated form (PR12) where the V1, V2 and V3 regions were removed. In contrast to previously published work [1] these studies show that monomeric forms of envelope are capable of inducing antibodies specific for both linear and discontinuous epitopes. These antibodies are capable of neutralising HIV infectivity. The majority of neutralising antibodies were specific for epitopes within the V2 and V3 regions demonstrating the immunodominance of these regions in monomeric gp 120. Relatively few of the antibodies were specific for the CD4 binding site, suggesting that this region is poorly immunogenic. Immunisation of rats with the PR12 truncated protein did not significantly enhance the immunogenicity of the CD4 binding site. However, the immune response generated included antibodies capable of binding to diverse primary HIV-1 and HIV-2 envelope glycoproteins. We have shown that up to 30% of sera from HIV-1 infected individuals have antibodies that are capable of recognising conformation-dependent epitopes within the V1V2 region of the clone HXB10, suggesting the presence of conserved cross-reactive epitopes. Furthermore we have shown an association between the presence of V1V2 reactive antibodies and the neutralisation titre of the sera tested suggesting that antibodies to this region contribute to the cross-reactive neutralising response.

AIDS Vaccines

Historic control comparison of outcome for matched groups of patients undergoing endoluminal versus open repair of abdominal aortic aneurysms.

PURPOSE: Currently no randomized studies show the relative morbidity and mortality of the open and endoluminal methods of abdominal aortic aneurysm (AAA) repair. The aim of this study was to analyze the outcome of two matched groups of patients with AAA, one undergoing open repair and the other undergoing endoluminal repair. METHODS: Two groups of patients who had undergone repair of AAA by open technique (group 1) or by endoluminal methods (group 2) were compared. A historic control cohort of 27 patients was selected from 56 consecutive patients who underwent open repair of AAA between January 1991 and February 1992. Patients considered unsuitable for the endoluminal method on the basis of computed tomography and aortography were excluded (n=29). Between May 1992 and November 1994 prospective data were recorded for 62 consecutive patients who underwent endoluminal repair by tube or bifurcated endografts. Twenty-eight patients who had been specifically referred for endoluminal AAA repairs because of preexisting severe medical comorbidities were excluded. Six of the endoluminal cases had failure, requiring conversion to open operation, and were excluded for separate analysis, leaving 28 patients in group 2. Patients in both groups were thus fit and suitable for either open or endoluminal repair and were comparable in relation to age, sex, risk factors, dimensions, and form of AAA. RESULTS: The mean values for operation time, blood loss, intensive care stay, and hospital stay for group 1 and group 2 were 2.6 versus 3.1 hours, 1422 versus 873 ml,* 1.8 versus 0.7 days,* and 12.4 versus 11.1 days, respectively (*p<0.05). Local/vascular complications occurred in 15% of patients in group 1 compared with 25% in group 2 (p=0.55), whereas remote/systemic complications occurred in 37% and 29%, respectively (p=0.3). Five of 28 patients in the endoluminal group had complications requiring early operative repair (n=3) or late revision (n=2). When comparison was made on an intention-to-treat basis (with failed procedures included), the incidence of local/vascular complications was significantly greater for endoluminal repair (p=0.047). CONCLUSIONS: The incidence of systemic/remote complications was similar for the two groups in spite of significantly less blood loss and shorter intensive care unit stay with endoluminal repair. The incidence of local/vascular complications had a tendency to be higher for endoluminal compared with standard open method (and was significantly greater if failed procedures were included). In this early experience with prototype devices, patients who were medically suitable for open surgical procedures did not derive benefit from the less invasive endoluminal technique with respect to duration of operation, length of hospital stay, or perioperative morbidity and mortality. On the other hand, because they also did not have worse outcome, a randomized study is now justified in this group.

Age Factors

Early experience with transfemoral endovascular aneurysm management (TEAM) in the treatment of aortic aneurysms.

OBJECTIVES: To evaluate the early experience with transfemoral endovascular aortic aneurysm management using the Endovascular Grafting System. DESIGN: Multi-centre prospective evaluation of the implantation procedure and early results (median follow-up 153 days). SETTING: Department of Surgery, University Hospital Utrecht, The Netherlands; Department of Surgery, University of Sydney, Australia; University of Leicester School of Medicine, Leicester, U.K., Department of Surgery, Karolinska Hospital, Stockholm, Sweden and Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital; Oxford, U.K. MATERIALS: 31 consecutive patients treated in 13 months. CHIEF OUTCOME MEASUREMENTS: Peri and postoperative morbidity and mortality in accordance with the recommendations of the Ad Hoc Committee on Reporting Standards. MAIN RESULTS: Graft placement was initially successful in all 31 patients. In one patient the endograft had to be replaced by a standard aortic tube graft because of extra graft flow in the aneurysm sac, and complaints of back pain. One patient died from multiple organ failure, 11 days after the operation. In three patients five severe adverse events were recorded. Breaks of the attachment system were encountered in two patients. These failures did not have severe clinical consequences for individual patients. CONCLUSIONS: Transfemoral Endovascular Aneurysm Management is a technically demanding procedure that requires special training in both catheter and surgical techniques. The potential for less operative morbidity when compared to conventional surgery and the prospect of technical improvements in graft and introduction system design will make TEAM an important tool in aneurysm management in the near future.

Aged

No additional benefit from laser in balloon angioplasty of the superficial femoral artery.

OBJECTIVES: To evaluate the efficacy of the addition of plaque ablation by hot-tip laser to balloon angioplasty. DESIGN: Prospective randomised clinical trial. MATERIALS AND METHODS: Patients with either occlusion orf > 50% diameter stenosis less than 3 cm in length in the superficial femoral artery, and with two or three calf vessel run-off were eligible and randomised to receive either balloon angioplasty alone or with laser assistance. Treatment failure in follow-up was defined as reocclusion or recurrence of greater that 50% stenosis at the site of angioplasty. RESULTS: Ninety limbs (82 patients) were entered into the study. Forty-four patients had mild claudication, 32 more severe symptoms and 6 rest pain or ulceration. More patients with diabetes (5 of 5, p = 0.04, Fisher's exact test) and occlusions (16 of 22, p < 0.05, chi(2)) were randomised to the laser group. Initial technical success was obtained in all lesions. The median duration of follow-up was 1 year. Failure occurred in 40 limbs during follow-up. Three segments, all with initial occlusions and undergoing laser angioplasty re-occluded within 2 days, one requiring immediate thrombectomy. Another 20 limbs underwent further intervention. Overall success (+/- S.D.) (Kaplan-Meier) at 1 year was 67% (+/- 5%) and at 2 years 43% (+/- 7%). Only increased age, initial occlusion, female sex, and not smoking were significantly (p < 0.05, Cox's proportional hazards) associated with failure; on multivariate analysis, age and occlusion were the best independent predictors. There was no significant difference (p > 0.05) in outcome between limbs undergoing laser assisted balloon angioplasty and balloon alone either overall of within the stenosis or occlusion subgroups. CONCLUSIONS: This study found no significant benefit was gained by the addition of laser to balloon angioplasty and that the long term success was modest for lesions considered to be suitable for angioplasty.

Aged

A prospective study of anatomico-pathological changes in abdominal aortic aneurysms following endoluminal repair: is the aneurysmal process reversed?

AIM: The aim of this prospective study was to analyse early anatomico-pathological changes in abdominal aortic aneurysms (AAA) following endoluminal repair to determine if the natural history of continued expansion of AAA is reversed. MATERIALS AND METHODS: Sixty-seven of 85 patients undergoing endoluminal AAA repair between May 1992 and August 1995 had their operations prior to the end of February 1995 and were potentially available for follow up at 6 months or longer after operation. Excluded were: patients with failed endoluminal repairs (n = 14), patients who died within 6 months of operation (n = 5), patients with anastomotic AAA (n = 1), leaving 47 patients in the study group. Based on contrast enhanced CT performed preoperatively, within 10 days of operation and 6, 12 and 18 months after operation patients were divided into two groups: those in whom the AAA maximum transverse diameter (MTD) decreased Group I (n = 39) and those in which it increased Group II (n = 8). The following parameters were analysed: diameter of the supra coeliac aorta, MTD and the dimensions of the proximal and distal necks of the AAA plus extravasation ("leak") of contrast into the aneurysmal sac. RESULTS: Leak of contrast was seen in 0 of 39 patients in Gp I and 5 of 8 patients in Gp II. Patients in Group I experienced a progressive diminution in AAA mean MTD. The diameters of the proximal and distal necks increased but there was no shortening of the length of the necks in this group. In Group II the AAA MTD was dependent on whether or not the aneurysmal sac was isolated from the circulation. The diameter of the proximal and distal necks increased irrespective of this fact. CONCLUSION: We conclude that in early follow up AAA which diminish in diameter following endoluminal repair remain isolated from the general circulation. Co-incident with this decrease in AAA diameter, the proximal and distal necks increase in diameter but do not undergo any shortening in length. This paradoxical increase in neck diameter, was not progressive in the period of follow-up.

Aged

Hickman catheters: left-sided insertion, male gender, and obesity are associated with an increased risk of complications.

BACKGROUND: Semipermanent tunnelled silicone rubber Hickman catheters are widely used to provide durable central venous access for patients with cancer or haematological disease. AIMS: To document the frequency and severity of Hickman catheter related adverse events and to identify predisposing factors. METHODS: A retrospective review was undertaken of 153 sequential Hickman catheters inserted into patients receiving treatment for cancer or haematological disease. All Hickman catheters were inserted percutaneously in a radiology department under local anaesthesia and fluoroscopic control. The exact position of the catheter tip was determined by reviewing post-insertion radiographs. RESULTS: The median duration of catheter use was 55 days (range one-650). Complications led to the removal of 32% of catheters. Exit site infection complicated 22% of catheters, septicaemia 7%, migration or dislodgment 7%, and venous thrombosis 8%. Complications were more common in male patients (exit site infection and catheter loss), in patients with acute leukaemia (septicaemia) and in obese patients (catheter migration). Left sided catheters caused more venous thrombosis and were more likely to malfunction or block. Left sided catheters required removal more frequently than right sided catheters. Termination of the Hickman catheter within the high superior vena cava (SVC) resulted in loss of function earlier when compared to termination with the low SVC or right atrium (RA). CONCLUSIONS: Right-sided Hickman catheters terminating in the low SVC/RA offer the best chance of durable function. The use of subcutaneously tunnelled catheters in obese patients poses unique problems with catheter migration. Vigilance in the placement and care of Hickman catheters remains essential.

Catheterization, Central Venous

Met-11 of HLA class II DP alpha 1 first domain associated with onchocerciasis.

Human infection with the pathogenic tissue nematode Onchocerca volvulus may result in a spectrum of clinical manifestations or in a putatively immune condition. A methionine at amino acid position 11 of the HLA class II DP alpha 1 chain correlates with the occurring disease after infection (relative risk 3.3). The alternative alanine at position 11 is, conversely, associated with protection from disease ("relative protection' 3.5). DPA1*0301 is associated with the localized form of disease after O. volvulus infection.

Amino Acid Sequence

[Ultrasonic pregnancy diagnosis (B-mode) in sheep. 2. Comparative studies using transcutaneous and transrectal pregnancy diagnosis].

The aim of this study was to check the earliest time for the ultrasonic pregnancy diagnosis in flock management of sheep after finishing the mating season. Therefore a transcutaneous pregnancy diagnosis (5 MHz) took place on a total of 1060 German merino-mutton sheep between day 10 and 90 after mating (a.m.) and a transrectal diagnosis (5 MHz) took place on a total of 1442 German merino-mutton sheep between day 10 and 70 a.m. At the beginning of the third week a.m. the accuracy of transrectal diagnosis was over 95% and increased to 100% on day 35 a.m. At that time the accuracy of transcutaneous diagnosis was 80% and reached 100% on day 60 a.m. Considering the reached accuracies the pregnancy diagnosis should not take place before day 35 after the end of the breeding season. After day 35 a.m. it is advisable to combine the transcutaneous and the transrectal pregnancy diagnosis. That means that at first all animals are examined by transcutaneous sonography and in the second step the so-called "non-pregnant sheep" are checked by transrectal ultrasound. From the beginning of the third month a.m. a single transcutaneous pregnancy diagnosis is sufficient.

Animals

Predicting outcomes in thoracic outlet syndrome.

OBJECTIVE: To test the hypothesis that somatosensory evoked potentials (SEP) and results of arterial photoplethysmography (PPG) predict outcome after surgery for thoracic outlet syndrome. DESIGN: A retrospective case series which correlated surgical outcome with preoperative SEP and PPG results using Fisher's exact test. PPG results were considered abnormal when there was complete loss of arterial pulsation, and SEP results when amplitudes were reduced and latencies delayed. SETTING: Royal Prince Alfred Hospital, between March 1984 and February 1992. PATIENTS: Forty-six consecutive patients with clinically diagnosed thoracic outlet syndrome were admitted for surgery; sixteen underwent bilateral operations (total of 63 limbs). INTERVENTIONS: After SEP and PPG tests, all patients underwent thoracic outlet decompressive surgery--excision of the first rib, of the cervical rib (where present), and of other congenital anomalies associated with thoracic outlet syndrome--by the axillary approach. MAIN OUTCOME MEASURES: Surgical outcome was graded as good when symptoms improved and the patient returned to work or pre-illness activities. It was graded as poor when symptoms remained unchanged or worsened, or when there was continued inability to work or engage in usual activities. RESULTS: The follow-up period ranged from 1.9-9.8 years (mean, 5.7 years). Significantly more limbs with abnormal SEP or PPG results had a good outcome (49 of 53 limbs; 93%) than limbs with normal SEP and PPG results (six of 10 limbs; 60%) (P = 0.02). CONCLUSIONS: Abnormal SEP and PPG results correlated with a better postsurgical outcome. These tests may therefore aid in determining prognosis of surgery for thoracic outlet syndrome.

Adolescent

Intestinal obstruction promotes gut translocation of bacteria.

PURPOSE: Translocation of enteric organisms has been implicated as a possible source of sepsis in susceptible patients. Animals studies have suggested that intestinal obstruction promotes bacterial translocation from the gut lumen. The aim of this study was to study the prevalence of bacterial translocation in patients with and without intestinal obstruction. METHODS: Serosal scrapings, mesenteric lymph nodes, and peripheral blood cultures were obtained from 254 patients. Scrapings and nodes were homogenized and incubated aerobically and anaerobically. Full-thickness biopsies underwent villous height analysis. The clinical course was followed for at least six weeks. RESULTS: Bacterial translocation to mesenteric nodes occurred more frequently in patients with large bowel obstruction than in patients without obstruction (14 of 36 patients vs. 16 of 218 patients; P < 0.001). Both aerobic and anaerobic bacteria were found to translocate. The more distal the obstruction, the more likely anaerobic bacteria were to be identified. Translocation of bacteria predisposed to postoperative septic complications (P < 0.05). Villous height was not related to bacterial translocation. CONCLUSIONS: Gut translocation of bacteria is more common in patients with intestinal obstruction, and its association with septic complications appears to be of clinical significance.

Adult