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A Wilkinson

Publications and source records attributed to A Wilkinson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Impact of the New Deal on vascular surgical training.

The rapid development and technological advances in vascular surgery have provided the impetus for the establishment of dedicated pure vascular surgical services. It remains unclear whether all vascular surgery will be provided by such units in the future or whether several district general hospitals will combine resources and provide dedicated vascular on-call rotas between surgeons on separate sites. Training in vascular surgery is also changing rapidly. A modular training scheme encompassing three levels of training has been recommended (1). Some of the training will only be performed in large training units, but there remains a requirement for general surgeons to be exposed to some vascular surgery during their training. The "New Deal' for junior doctors has imposed limits on the amount of hours worked during a week. Junior doctors should not on average be contracted for more than 72 hours a week or work more than 56 (2). The maximum on-call rota which fulfils these criteria is a 1 in 4 on-call with no early starts, late finishes and no prospective cover. Allowing for holidays, study leave, early starts and late finishes a 1 in 5 or 1 in 6 rota system is required. Implementation of the Calman report in higher specialist training would reduce the time spent in training at high specialist level to perhaps five years. In a modular training programme in vascular surgery there may be as little as one year Level II training spent in vascular surgery or perhaps two years if the candidate opted to have vascular surgery as their only sub-specialty. In an attempt to assess the impact of the New Deal and the Calman report on vascular surgical training we have assessed the exposure to vascular surgical procedure of hypothetical trainees on a 1 in 6 rota.

Education, Medical, Graduate↗
PubMed1995

Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not correlate with acute transplant rejection.

TH1 cytokines, including gamma-interferon (IFN), are critical in the initiation and progression of allograft rejection. As interleukin (IL)-12 up-regulates gamma-IFN, we assessed the role of IL-12 in human transplant rejection. Twenty renal allograft fine-needle aspirates from 19 patients were obtained, evaluated in the standard fashion, and assessed for gamma-IFN and IL-12p40 subunit mRNA levels using nested reverse transcriptase polymerase chain reaction. Ten aspirates demonstrated acute rejection by clinical criteria, and 9 of the 10 aspirates contained gamma-IFN while only 3 demonstrated IL-12; there were no distinguishing characteristics for these 3 patients with regard to therapy, or time of onset and severity of rejection. Seven patients without clinical or morphologic rejection failed to demonstrate gamma-IFN or IL-12. Three patients had discrepant findings; there was no morphologic rejection, yet all 3 patients contained gamma-IFN and 1 patient demonstrated rejection on subsequent biopsy. However, only 1 aspirate exhibited IL-12 and this patient had no documented subsequent rejection. This study confirms the association of gamma-IFN mRNA with acute rejection. In contrast, IL-12 mRNA does not appear to play a key role early in the rejection process.

Acute Disease↗
PubMed1995

Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism.

Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.

Adult↗
PubMed1995

Immunolocalization of hepatic metastases of human colonic cancer by chimeric anti-TAG72 antibody in SCID mice.

TAG72 is a well-characterized, human tumor-associated antigen present in > 85% of human colonic cancers. In this study, we established an animal model of hepatic metastases of human colonic carcinoma. The high-mucin variant cell line, designated HM7, was derived from the human colonic carcinoma cell line LS174T. Following intrasplenic injection, HM7 was able to induce much greater hepatic metastases in SCID mice compared to its parental cell line LS174T. Numerous hepatic metastases were evident 18 days subsequent to the intrasplenic injection of tumor cells. Using the chimeric anti-TAG72 antibody ccM4, immunohistochemistry demonstrated strong expressions of the TAG72 antigen in these metastases. Our biodistribution and imaging data also showed that the radiolabelled ccM4 antibody was able to localize hepatic metastases in the SCID mice. Based upon these findings, w anticipate that the herein described SCID mouse model will prove most useful in studying hepatic metastases of human colonic carcinoma by using anti-TAG72 therapeutic immunoreagents.

Adenocarcinoma↗
PubMed1995

Loin pain hematuria syndrome: pain relief with intrathecal morphine.

Loin pain hematuria syndrome (LPHS) is characterized by hematuria and incapacitating loin pain. The pain experienced with LPHS is, in general, extremely difficult to treat. Many surgical and pharmacologic therapies have been directed at LPHS pain without success. This report documents successful pain control in a patient with LPHS using long-term intrathecal morphine delivered via an implantable pump. Intrathecal narcotic therapy may provide pain relief for the chronic pain of LPHS.

Adult↗
PubMed1995

Intrarenal extramedullary erythropoiesis in renal allograft fine-needle aspirates.

Recombinant human erythropoietin (rhEPO) is widely used in patients with end-stage renal disease and occasionally in renal allograft recipients to correct anemia. Red blood cell production is markedly increased by rhEPO; however, no extramedullary erythropoiesis (EME) has been associated with this hormone. We observed intrarenal EME in five allograft fine-needle aspirates performed for reduced graft function in four patients between 3.7 and 7 weeks following transplantation. These four patients received rhEPO during dialysis and three resumed rhEPO therapy after transplantation; all four remained anemic. Donors were between 13 months and 13 years of age, with one pediatric and three adult recipients. Aspirates with apparently incidental EME contained all stages of red blood cell precursors, but these cells were not observed in corresponding peripheral blood samples. The hematopoietic cells could be readily distinguished from cells of lymphoid origin. There were no correlations between intragraft EME and aspirate or clinical diagnosis referable to renal dysfunction. Aspirates performed prior to 3.7 weeks or after 7 weeks did not demonstrate EME. These data suggest that endogenous EPO and rhEPO in anemic patients receiving pediatric renal allografts may activate red blood cell precursors in the young graft, inducing intrarenal EME. Recognition of this entity is important to distinguish it from immune activation or malignancy within the donor organ.

Adult↗
PubMed1995

Saphenous vein forearm grafts and gortex thigh grafts as alternative forms of vascular access.

To compare the survival and complication rates of saphenous vein forearm grafts and gortex thigh grafts. Retrospective study over a twelve-year period with review of case-notes. Saphenous vein forearm grafts were constructed in 17 males and 12 females, mean age 61 years and gortex thigh grafts in 24 males and 22 females (49 grafts), mean age 49 years. Grafts were the primary form of access in 9 patients in each group. Follow-up was 45.6 and 135.2 patient years on dialysis for forearm grafts and thigh grafts respectively. One-year total survival was 89.4% (89.4% at 2 years and 71.5% at 3 years) and 84.9% (82.3% at 2 years and 70.4% at 3 years) for saphenous vein forearm grafts and gortex thigh grafts respectively. The overall complication rates were 0.22 and 0.61 per patient year on dialysis for saphenous vein forearm grafts and gortex thigh grafts respectively. Thrombosis occurred in 10% and 52%, infection in 0% and 35% and no complications in 62% and 24% of saphenous vein forearm grafts and gortex thigh grafts respectively. Both saphenous vein forearm grafts and gortex thigh grafts can provide satisfactory vascular access. The survival is similar at one year but gortex thigh grafts have a higher complication rate.

Adult↗
PubMed1994

Gamma-interferon gene expression in human renal allograft fine-needle aspirates.

Cytokines appear to play a major role in acute transplant rejection (AR); however, the specific cytokines initiating AR are not known. To investigate gamma-interferon messenger RNA (mRNA) as a key factor in AR induction, we performed reverse transcription-polymerase chain reaction (RT-PCR) on renal allograft fine-needle aspirates (FNA). Fifteen FNA from 15 patients were processed and interpreted in the standard fashion, the percent of tubular cells with MHC class II expression (DR) quantitated, and aliquots of FNA obtained for RT-PCR. RT-PCR was performed with primers to gamma-IFN with cyclophylin and insulin primers as controls. Retrospective clinical diagnoses were made for each FNA sample. Following RT-PCR, all FNA and FNAs from control normal and AR nephrectomy specimens had cyclophylin present, and in the 9 samples tested insulin was absent. Five patients had AR clinically and by FNA criteria; all 5 had elevated DR and gamma-IFN mRNA present in FNA. Five patients had tubular necrosis or cyclosporine toxicity clinically, and FNA without immune activation or elevated DR and negative gamma-IFN mRNA. Two patients had immune activation by FNA with elevated DR; both FNA expressed gamma-IFN mRNA by Southern blot, one only weakly, and both patients subsequently developed clinical AR. Two patients had recently treated AR, one with persistent DR elevation without-immune activation and negative gamma-IFN mRNA in FNAs. This study demonstrates that RT-PCR can be performed with renal allograft FNA samples. The findings suggest intragraft gamma-IFN mRNA expression occurs in active AR preceding clinical AR, thus defining incipient AR. Detection of gamma-IFN mRNA may offer an early diagnostic tool for detection of AR.

Base Sequence↗
PubMed1994

Alaproclate acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow.

We studied the effect of alaproclate [2-(4-chlorophenyl)-1,1-dimethyl 2-aminopropanoate] on the N-methyl-D-aspartate (NMDA)-induced changes in membrane potential and intracellular free Ca++ in cerebellar granule cells by using the fluorescent indicators DiBaC4(3) and fura-2, respectively. The NMDA-induced responses were blocked by the 5-hydroxytryptamine reuptake blocker alaproclate in a noncompetitive manner with an IC50 value of 0.3 microM. The effect of alaproclate was stereoselective because the S-(-)-enantiomer was more potent than the R-(+)-enantiomer. The inhibitory response was rapidly reversed if alaproclate was removed by perfusion. The same was the case with the reversible noncompetitive NMDA receptor antagonists dextromethorphan, dextrorphan, amitriptyline and desipramine. The inhibition caused by the noncompetitive antagonist dizolcipine could not be reversed by perfusion. The glycine-sensitivity of the NMDA response was unaffected by alaproclate, and high concentrations of glycine were unable to reverse the inhibition of alaproclate. Alaproclate also did not affect the sensitivity of the responses to Mg++. The results suggest that alaproclate, which has previously been in clinical trials for depressive illness, acts as a reversible noncompetitive antagonist of the NMDA receptor.

Alanine↗
PubMed1993

High-affinity chimeric anti-(colorectal carcinoma) antibody correlated to enhanced tumor targeting in biodistribution and imaging.

The genetically engineered chimeric cB72.3m4 and cB72.3m12 antibodies recognize the same tumor-associated TAG72 antigen. The high-affinity cB72.3m4 antibody had an approximately 18-fold higher affinity constant for the TAG72 antigen than the low-affinity cB72.3m12 antibody. The relationship between antibody affinity and tumor targeting was studied by using these two antibodies. In biodistribution and imaging studies in athymic mice bearing LS174T human colon cancer xenografts, the radiolabelled high-affinity cB72.3m4 antibody was rapidly cleared from the blood, whereas the low-affinity cB72.3m12 antibody had slower blood clearance. The data showed that the high-affinity cB72.3m4 antibody appeared to localize more in tumors (based on tumor:normal-tissue ratios) than did the low-affinity cB72.3m12 antibody, and enhanced the target-to-nontarget image contrast. This study provides evidence that the high-affinity chimeric antibody cB72.3m4 may be useful in both immunodetection and immunotherapy of cancer.

Animals↗
PubMed1991

Evaluation of fine-needle aspiration biopsy in the diagnosis of renal transplant dysfunction.

Fine-needle aspiration biopsy (FNAB) was performed in 41 renal transplant patients to assess its value in the diagnosis of the cause of graft dysfunction. The procedure was used on 71 occasions, and in each case a clinical diagnosis was made and compared with the cytological diagnosis made independently by a pathologist. When available, core biopsy histopathology was used to confirm the final diagnosis. Fifty-seven (80%) of the aspirates yielded adequate material. A clinical diagnosis of acute cellular rejection (ACR) was made in 21 patients, 18 (78%) of whom showed confirmatory immune activation on FNAB. The clinical diagnosis of either acute tubular necrosis (ATN) or cyclosporine toxicity was confirmed in 31 (91%) of 34 aspirates. In eight aspirates, the cytological diagnosis was different than that made clinically. Humorally mediated vascular rejection, and lymphocytosis secondary to causes other than rejection, such as viral infection, were considered as possible causes of this discrepancy. Provided that adequate samples are obtained. FNAB is valuable in the clinical management of renal transplant patients. Its accuracy should not be overestimated and the results obtained should be evaluated in the light of the overall clinical picture.

Biopsy, Needle↗
PubMed1991

Differentiation of cytomegalovirus infection from acute rejection using renal allograft fine needle aspirates.

Cytomegalovirus (CMV) infection is an important cause of renal allograft dysfunction and may be difficult to distinguish from acute transplant rejection both clinically and histologically. To establish the early diagnosis of CMV infection, we used immunohistochemical staining with antibodies against CMV early nuclear protein (CMV-A) and histocompatibility leukocyte class II antigen (DR) in renal transplant fine needle aspirates. Fifty-eight aspirates from 27 patients were assessed, 53 for CMV-A and 53 for DR. Positive staining was defined as greater than or equal to 35% stained tubular cells for CMV-A and greater than or equal to 30% stained tubular cells for DR. Clinical diagnoses were made retrospectively without using the information obtained from aspirate diagnoses. CMV-A staining was negative in 44 aspirates, none at the time of CMV infection. CMV-A was positive in nine aspirates, seven during CMV infection (78%, P less than 0.00001 versus CMV-A negative). DR staining was never present in the absence of acute rejection. All aspirates performed during acute rejection had positive DR staining (P less than 0.00001 versus DR negative). Aspirates with acute rejection comprised 80% of all DR-positive aspirates, whereas those with CMV infection included only 13%. The percent CMV-A staining increased with CMV disease progression; DR staining decreased after successful treatment of acute rejection. These data demonstrate that CMV-A staining is associated with CMV infection whereas DR staining is not. DR staining is specifically related to acute rejection. CMV-A and DR staining of fine needle aspirates is a potentially valuable diagnostic tool to distinguish rapidly between CMV infection and acute transplant rejection as the etiology of renal allograft dysfunction.

Antigens, Viral↗