Search PubMed⌕ Search

Biomedical subjects

J R Chapman

Publications and source records attributed to J R Chapman.

At least 19 recordsLinked to original sources
PubMed2003

Optimizing the long-term outcome of renal transplants: opportunities created by sirolimus.

This review focuses upon the sirolimus-based cyclosporine elimination studies and the light they shed on choice of the best long-term immunosuppressive strategy for managing the balance between prevention of loss of grafts from antigen specific immune responses or from chronic nephrotoxicity. The underlying strategy of both cyclosporine elimination studies was to treat patients with a uniform therapy for the first 3 months and then wean off the cyclosporine therapy in one cohort. The Phase II study was conducted in 246 recipients in 17 centers in the USA and Europe. Thus 97 patients were treated with full-dose cyclosporine, fixed-dose sirolimus and corticosteroids, and 100 patients received reduced-dose cyclosporine and trough concentration controlled sirolimus with corticosteroids until 3 months when the dose of cyclosporine was tapered progressively. The phase III study was undertaken in 525 patients in 57 centers in Australia, Canada and Europe with randomization for cyclosporine elimination undertaken at 3 months and implemented over the next 4-6 weeks. The primary outcome of renal function was better in the elimination arms of both studies and, in the phase III study, continued to improve for up to 2 years. Both studies demonstrated better renal function, equivalent patient and graft survival and no difference in acute rejection rates. These studies have shown that one of the successful strategies for improving the longer term graft survival rates includes the continuous use of sirolimus and steroids, without calcineurin inhibitors.

Adult↗
PubMed2002

Deleterious effect of smoking on healing of open tibia-shaft fractures.

We retrospectively reviewed a prospectively followed cohort of 105 patients with 110 open tibia fractures treated with external fixator or intramedullary nail to determine whether smoking affects fracture healing. Severe open tibia-shaft fractures treated at a tertiary-care medical center were included. Patients with type II, IIIA, or IIIB tibia fractures were eligible. Treatment for all patients was similar, except that they were randomized to receive external fixator or intramedullary nail. Time to fracture healing was the main outcome measurement. Smokers had a union rate of 84% (52/62), and nonsmokers had a union rate of 94% (45/48), P = .10. For smokers in one arm of the study, time to union was significantly longer (P = .01), and there were more complications (P = .04). Smoking decreased unions, slowed healing, and increased complications.

Adolescent↗
PubMed2001

Effect of histological damage on long-term kidney transplant outcome.

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.

Adult↗
PubMed2001

Role of cathepsin D in prostatic cancer cell growth and its regulation by brefeldin A.

We investigated a possible relationship between brefeldin A (BFA), an antibiotic, and cathepsin D (Cat.D), a lysosomal protease, in prostate cancer proliferation. Effects of BFA (30 ng/ml) were examined on the growth of three human prostatic cancer cell lines, PC-3, DU-145, and LNCaP cells. Its effect on Cat.D in these cancer cells was assessed by Western blots and compared with Cat.D expressed in clinical prostate specimens (n = 55). BFA profoundly (> 70%) inhibited the growth of all three cancer cell lines. Western blots revealed that expression of procathepsin D (Pro.Cat.D) was markedly increased with BFA, whereas actively proliferating (control) cells greatly exhibited mature Cat.D. Analysis of prostate specimens then showed predominant Pro.Cat.D expression in non-cancerous tissues while also showing enhanced expression of mature Cat.D in all cancer specimens. Therefore, BFA-induced growth inhibition in prostatic cancer cells is associated with a blocking of Cat.D maturation (activation), suggesting a possible role of Cat.D in prostate cancer proliferation/development.

Antifungal Agents↗
PubMed2001

Factors in older cadaveric organ donors impacting on renal allograft outcome.

Transplantation of renal allografts (RA) from older donors has become more common, despite conflicting data on outcome between reports from large series versus individual centres. Factors other than donor age per se may contribute to RA outcome. The outcome of RA procured from 114 older donors over 55 yr of age in NSW, between 1990 and 1997, was analysed. Corresponding donor factors, including demographics, medical history, inotrope use, major hypotension and findings at procurement, were also analysed. Of the potential RA, 8% were discarded and the remainder transplanted. Factors significantly associated with renal discard were pre-transplantation donation biopsy abnormality (p < 0.001) and a history of cardiovascular (CV) disease in the donor (p < 0.02). Donor aortorenal atherosclerosis (AS; p < 0.09) and a donor age of 65 yr or older (p < 0.08) were common in the discard group. The never function rate was 7.6% and was associated with a history of a discarded partner kidney (p < 0.05). The delayed graft function rate was 33% and was associated with a history of donor CV disease. At a median follow up of 5 yr, the death censored allograft failure rate was 24%. Allograft failure was associated with a history of donor hypertension (p < 0.05). Donor AS (p < 0.7) tended to have been more common in the allograft failure group. A number of cadaveric organ donor factors documented at procurement may be associated with inferior outcome of RA. These include biopsy abnormality, history of donor CV disease and history of donor hypertension. A donor age of 65 yr or older or significant visible aortorenal AS may also be factors. This retrospective review of kidneys procured from 114 older cadaveric organ donors identifies factors apart from donor age, which may have a negative impact on both allograft utilisation and outcome. Theses factors include renal biopsy abnormality, history of donor CV disease, discard of a partner kidney and donor hypertension. Visible AS in the donor aorta documented at renal procurement may also be a factor.

Aged↗
PubMed2001

Diagnosis of kidney transplant obstruction using Mag3 diuretic renography.

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long-term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium-99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n = 21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n = 43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6 +/- 18.9 vs. 81.6 +/- 5.4%, p < 0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9 +/- 4.1 vs. 3.6 +/- 1.5 min, p < 0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to < 75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold-up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of > 5 min and a TTB of > 7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.

Adult↗
PubMed2000

Posttransplant cataract: lessons from kidney-pancreas transplantation.

INTRODUCTION: Cataract is a major cause of visual disturbance after transplantation. Although corticosteroid therapy has been linked with posterior subcapsular cataract, its natural history in the cyclosporine era is not well understood. METHODS: Baseline and regular postoperative slit-lamp biomicroscopy and ophthalmic examinations (n=432) were performed in 108 eyes of simultaneous kidney/pancreas (SPK) recipients (n=54) for up to 10 years after transplantation. Triple therapy immunosuppression of cyclosporine, azathioprine, and prednisolone was used. RESULTS: Cataract was present in 40% of eyes at simultaneous kidney/pancreas associated with duration of diabetes, lower insulin dose, and the use of pretransplant hemodialysis (P<0.05-0.01). Cataract became increasing more common 2 years after simultaneous kidney/pancreas, and lens abnormalities were virtually universal at 6-10 years by slit lamp biomicrosopy. The instantaneous hazard rate for new cataract formation was highest within the first 2 years and remained abnormal for the study duration. Nuclear and posterior subcapsular cataract increased significantly after transplantation (P<0.05) and were the predominant types of cataract presenting late. Risk factors for posttransplant cataract formation included older age and high-dose pulse methylprednisolone dose. Visual acuity was reduced by severity of cataract grade, presence of combined nuclear and subcapsular cataract, retinal hemorrhage and underlying diabetic retinopathy (P<0.05-0.001). Cataract formation imposed significant additional impairment of visual acuity above that of diabetic retinopathy. Cataract surgery was undertaken in 14% of eyes, improving visual acuity from mean decimalized score of 0.28 to 0.43, P<0.01 but did not normalize it to the noncataract level of 0.72. CONCLUSION: Transplantation substantially increases all types of cataract, and is highly prevalent by slit lamp examination. High-risk patients are older and diabetic, and received hemodialysis and pulse corticosteroid therapy. In contrast to older studies using high-dose corticosteroid and azathioprine, the pattern of cataract in the cyclosporine era is different with broader cataract types, a weaker association with corticosteroids and a progressive course. Regular screening of visual acuity and appropriate surgery for posterior subcapsular or severe cataract are recommended.

Adult↗
PubMed2000

Progression of macrovascular disease after transplantation.

INTRODUCTION: Cardiovascular and cerebrovascular disease are major causes of morbidity and mortality after kidney transplantation. The aim of this longitudinal study was to examine the natural history of carotid plaque and to determine risk factors for the progression of vascular disease in uremic, type 1 diabetic patients who received a combined kidney and pancreas transplant. METHODS: Carotid artery (n=765) and lower limb vascular duplex scanning (n=656) were prospectively undertaken in 82 recipients before transplantation, at 6 months, and then at annual intervals for up to 10 years. Plaque in the internal carotid artery (ICA), external carotid artery, and common carotid artery was classified by type, location, extent, and degree of functional obstruction, and evaluated using multivariate analysis. RESULTS: Carotid plaque was present in 22.5% of patients at initial scanning, but increased to 56.6% by 7-10 years after transplantation, especially in the ICA and common carotid artery. Both the severity and extent of plaque increased, and plaque became more complex and heterogeneous with time after transplantation (P<0.001). Carotid plaque was associated with older age, current cigarette smoking, hyperphosphatemia, hypoalbuminemia, duration of pretransplantation dialysis, and presence of lower limb plaque (P<0.05-0.001). The severity of carotid plaque increased in older, hypertensive recipients and was associated with metabolic acidosis and hyperphosphatemia (all P<0.05). Severity of ICA disease correlated with disease in the contralateral ICA (r=0.57, P<0.001) and femoral arteries (r=0.42, P<0.001). Paradoxically, each carotid artery progressed independently of the other. ICA disease severity progressed when heterogenous, calcified, or new plaque was present on scanning, and with reduced renal transplant function (P<0.01-0.001). The mean ICA blood flow remained stable with time but was progressively impaired by hypertension, fasting hyperglycemia, and a lower prednisolone dose (P<0.05). Cerebrovascular events occurred in only four patients and were unrelated to carotid disease, implying relative plaque stability. CONCLUSION: Extensive carotid vascular wall abnormalities increased significantly despite kidney and pancreas transplantation. Initiation of plaque was associated with systemic factors, whereas progression of established plaque was largely influenced by local factors within the arterial wall.

Adult↗
PubMed2000

The anterior T-frame external fixator for high-energy proximal tibial fractures.

The authors' experience using anterior T-frame external fixation combined with percutaneous internal fixation for treatment of high-energy proximal tibial fractures is reported. Thirty-six patients (38 fractures) were reviewed who were treated during a consecutive 42-month period. Three patients died and one patient had an amputation for a Type IIIC open injury, leaving 20 males and 12 females with 21 closed and 13 open fractures (two Type II, seven Type IIIA, three Type IIIB, and one Type IIIC). The average followup was 26 months. Fractures united at a mean of 20 weeks. Ten secondary surgical procedures were planned, including seven antibiotic bead removals with autogenous bone grafting and three soft tissue coverage procedures. Nine (26%) complications were found, including one deep infection (septic arthritis) and three pin tract infections, and one each malunion, nonunion, refracture, knee stiffness requiring manipulation under anesthesia, and deep venous thrombosis. The average Knee Society score was 85 for pain and 83 for function. All patients achieved full knee extension and mean flexion was 125 degrees. The anterior T-frame external fixator with percutaneous internal fixation is a reliable method to stabilize these injuries. It is simple, inexpensive, and effective.

Adolescent↗
PubMed2000

Use of structural allografts in spinal osteomyelitis: a review of 47 cases.

OBJECT: The use of structural allografts in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. The authors have identified 47 patients over the last 3.5 years who underwent a surgical decompression and stabilization procedure in which fresh-frozen allografts were used after aggressive removal of infected and devitalized tissue. The patients subsequently underwent 6 weeks of postoperative antibiotic therapy (12 months for those with tuberculosis [TB]). METHODS: Follow-up data included results of serial clinical examinations, radiography, laboratory analysis (erythrocyte sedimentation rate and white blood cell count), and clinical outcome questionnaires. Of the original 47 patients (14 women and 33 men, aged 14-83 years), 39 were available for follow up. The average follow-up period at the time this article was submitted was 17 +/- 9 months (median 14 months, range 6-45 months). In the majority of cases (57%), a Staphylococcus species was the infectious organism. Predisposing risk factors included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and concurrent infections. During the follow-up period only two patients suffered recurrent infection at a contiguous level; both had a history of IVDA and one also had a chronic excoriating skin condition. No other recurrent infections have been identified, and no patient has required reoperation for persistent infection or allograft/hardware failure. CONCLUSIONS: It is the authors' opinion that the use of structural allografts in combination with aggressive tissue debridement and adjuvant antibiotic therapy provide a safe and effective therapy in cases of spinal osteomyelitis requiring surgery.

Adolescent↗
PubMed1999

Predictors of renal transplant histology at three months.

BACKGROUND: The quality of a damaged kidney, the complexity of the surgery, and the events in the first weeks after transplantation, such as delayed graft function (DGF) and acute rejection, may influence its histological appearance and long-term survival. The aim of this study was to evaluate the importance of these factors in predicting renal allograft histology at 3 months. METHODS: Prospective, protocol kidney biopsy specimens (n=112), obtained 3 months after transplantation, were scored for chronic damage by the Banff schema and evaluated by multivariate analysis against donor factors, implantation histology, prior recipient sensitization, ischemia, perioperative factors, and subsequent clinical events, such as DGF and acute rejection. RESULTS: Adequate samples were obtained in 102 of 112 biopsies and classified as chronic Banff grade 0 (n=22), grade I (n=56), grade II (n=23), or grade III (n=1). Acute Banff scores were minimal. DGF occurred in 49% and was the strongest predictor of tubulointerstitial damage at 3 months. DGF correlated with acute tubular necrosis on the implantation biopsy specimen and with the number of acute rejection episodes; DGF also correlated with the Banff grades of chronic glomerulitis, chronic interstitial fibrosis, and tubular atrophy scores (P<0.05-0.001) in the 3-month biopsy specimen. By multivariate analysis, chronic tubular atrophy was independently predicted by the presence of vascular disease in the donor biopsy specimen, DGF, and vascular rejection occurring within the first 3 months (P<0.05-0.001). Chronic interstitial fibrosis was unrelated to fibrosis in the donor biopsy specimen but was independently predicted by DGF, donor age, and vascular rejection (P<0.05-0.001). Vascular disease in the donor biopsy specimen correlated with chronic intimal thickening (r=0.36, P<0.01) and arteriolar hyalinosis score (r=0.54, P<0.001) on the 3-month biopsy specimen. Banff chronic intimal vascular thickening was independently predicted by donor biopsy specimen vascular grade, prior vascular rejection episodes, and renal cold ischemia time (P<0.05-0.01). There were no correlates with the mean cyclosporine (CsA) dose, blood levels, diagnosis of CsA toxicity, or cellular rejection within the first 3 months. CONCLUSIONS: This study has demonstrated that the quality of the donor organ at implantation was strongly predictive of subsequent renal histology in grafts functioning at 3 months. Vascular rejection and DGF had a significant long-term effect on graft damage, but cellular rejection and simple measures of CsA exposure did not.

Acute Disease↗
PubMed1999

Successful obstetric outcome after simultaneous pancreas and kidney transplantation.

A 34-year-old woman became pregnant two years after having a simultaneous pancreas and kidney (SPK) transplantation, necessitated by type 1 diabetes and end-stage renal disease. The pregnancy was uneventful until 30 weeks' gestation, when she developed pancreatitis and a worsening of mild hypertension. A healthy 1700 g boy was delivered by caesarean section at 34 weeks' gestation. This is the first report of a successful pregnancy after SPK transplantation in Australia.

Adult↗
PubMed1999

Mercaptoacetyltriglycine diuretic renography and output efficiency measurement in renal transplant patients.

Suspected urinary tract obstruction following renal transplantation presents a diagnostic dilemma. The purposes of this study were: (1) to establish a normal range of measurement of output efficiency (OE) in the renal transplant population, and (2) to assess prospectively the usefulness of OE in the setting of allograft obstruction. Twenty-two renal transplant patients with stable renal function and no evidence of hydronephrosis on serial ultrasound examination had a diuretic mercaptoacetyltriglycine scan with calculation of OE. Three renal transplant patients with confirmed graft obstruction were also studied. Standard qualitative and quantitative parameters as well as OE were calculated. The mean OE for the 22 normal renal transplant patients was 86.3%+/-3.7% (range: 77%-91%). OE values in the three obstructed patients were 59%, 68% and 75% respectively. It is concluded that OE should normally exceed 77% in renal graft recipients. OE is a promising means of diagnosing functional obstruction in these patients.

Adult↗