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Biomedical subjects

A S Lindblad

Publications and source records attributed to A S Lindblad.

15 recordsLinked to original sources

Studies of Pediatric Liver Transplantation 2002: patient and graft survival and rejection in pediatric recipients of a first liver transplant in the United States and Canada.

Studies of Pediatric Liver Transplantation (SPLIT) is a cooperative research network comprising 38 pediatric liver transplant centers in North America. Data from the 1092 patients who have received a first liver transplant since 1995 were analyzed for factors influencing patient survival, graft survival and acute rejection. The 3, 12, 24 and 36 month Kaplan-Meier estimates of patient/graft survival were 90.9/85.5, 86.3/80.2, 84.3/76.0, and 83.8/75.3% respectively. Univariate analysis identified initial diagnosis, type of graft (whole vs. living and cadaveric technical variant), growth failure and continuous hospitalization or ICU admission prior to transplantation as significantly influencing patient and graft survival. Subsequent multivariate analysis identified as risk factors for death: fulminant liver failure (RR = 3.05, p < 0.05), cadaveric technical variant grafts (RR = 1.95, p < 0.05), continuous hospitalization pre-transplant (RR = 1.79, p < 0.05), height deficit >2 s.d. from mean (RR = 3.22, p < 0.05). Risk factors for graft loss included: fulminant liver failure (RR = 2.27, p < 0.05), cadaveric technical variant grafts, (RR = 1.97, p < 0.05). Eleven percent of the 1092 patients were re-transplanted; vascular complications, particularly hepatic artery thrombosis (8.3% overall; 36.3% of graft failures), were responsible for the majority of re-transplants. Infection was the single most important cause of death (40 of 141, 28.4%) and was a contributing cause in 55 (39%), particularly with bacterial or fungal organisms. The cumulative Kaplan-Meier estimates of first rejection at 3, 12, 24 and 36 months were 44.8, 52.9, 59.1, and 60.3%. Initial immunosuppression with tacrolimus reduced the probability of rejection (RR = 0.62, p < 0.05). Eleven percent of rejections were steroid-resistant; chronic rejection led to 7 of 121 (5.8%) re-transplants. The SPLIT registry, in compiling data from a large number of centers, reflects the current outcomes for pediatric liver transplants in North America.

Adolescent↗

Studies of Pediatric Liver Transplantation: 2002 update. An overview of demographics, indications, timing, and immunosuppressive practices in pediatric liver transplantation in the United States and Canada.

Studies of Pediatric Liver Transplantation (SPLIT) was initiated in 1995 for the purpose of collecting comprehensive data from children undergoing liver transplantation. As of May 31, 2002, 1761 children were registered in SPLIT from 38 participating centers in the United States and Canada. This report focuses on the demographics, primary diagnoses, clinical indications for transplant, and probability of obtaining liver transplantation for the 1187 children receiving a liver transplant after registration in SPLIT. Demographic information is also provided for the 1092 children who received their first ever liver transplantation. For this cohort, we also describe immunosuppressive practices at the time of transplant, and how the use of different medications changes with time.

ABO Blood-Group System↗

A multicentre randomised double masked clinical trial of a new formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis.

AIM: To evaluate the safety and efficacy of a new topical cysteamine formulation, stable at room temperature, for the treatment of corneal cystine crystals in cystinosis. METHODS: 20 study subjects were enrolled in the safety study and 16 in the efficacy study. Both studies were randomised and double blind. The primary outcome for the safety study was the occurrence of predefined serious adverse reactions over 6 months and for the efficacy study the reduction of corneal cystine crystal score (CCCS) by 1.00 or more units on photographs graded by a reading centre using a standardised protocol. RESULTS: No study subject developed any serious adverse reactions. In the efficacy study, 47% of eyes receiving the standard formulation experienced a reduction in the CCCS of >/=1.00 after 1 year, while 7% of eyes on the new formulation experienced such a decrease (p=0.04). CONCLUSION: Although no serious adverse reactions were observed with either formulation, the new formulation was not as effective as the standard formulation.

Administration, Topical↗

Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis.

CONTEXT: Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. OBJECTIVE: To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. DESIGN: Prospective nonrandomized interventional trial performed from July 1997 to August 1999. SETTING: Clinical Center of the National Institutes of Health, Bethesda, Md. PATIENTS: Fourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.1 5 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. INTERVENTIONS: Discontinuation of specific anti-CMV therapy. MAIN OUTCOME MEASURES: Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. RESULTS: Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. CONCLUSIONS: Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.

AIDS-Related Opportunistic Infections↗

The Banff 97 working classification of renal allograft pathology.

BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

Acute Disease↗

The effects of treatment noncompliance on power in a 2 x 2 factorial design.

Clinical trials testing interventions that are available to the public and thus to potential participants must consider the impact of noncompliance on the power of the planned study to detect treatment differences. In long-term trials noncompliance may be assumed to vary over time. Increases in power of the F-test to detect differences in the proportion of participants responding to treatment in a 2 x 2 factorial design are observed when a simple, discrete, time-varying noncompliance model is compared to an assumption of immediate noncompliance. This increase holds in the presence of interaction and can become more substantial as trial duration lengthens or alpha level decreases.

Data Interpretation, Statistical↗

Recovery of renal function in continuous ambulatory peritoneal dialysis: a study of National CAPD Registry data.

From January 1981 to July 1988, the U.S. National CAPD Registry followed 23,771 patients on CAPD or CCPD for 3 months or more in 498 participating centers. Of these patients, 281 were deemed to have enough recovery of renal function to do without dialysis for at least 3 months. The median time on PD before recovery was 126 days in 138 patients treated only by PD from the start of dialysis. The median time to recovery in 106 patients was 238 days from the start of any chronic dialysis. A Cox model analysis revealed significantly (p less than 0.05) increased chances for renal function recovery in patients with systemic immunological diseases with renal involvement (relative risk for recovery [rr] = 2.48), patients with renal infarction related to renal vascular occlusion (rr = 4.13), and patients greater than 60 years of age compared to a younger group (rr = 1.72). However, patients greater than 60 and less than 21 experienced similar recovery rates. Reduced chances (p less than 0.05) for recovery were associated with diabetic glomerulosclerosis (rr = 0.25) and polycystic kidney disease (rr = 0.13). These findings show that renal function recovery rates in chronic hemodialysis and chronic peritoneal dialysis cannot be properly compared unless all risk factors (favoring or against recovery) are balanced, as in a prospective randomized trial.

Adult↗

Timing and characteristics of multiple peritonitis episodes: a report of the National CAPD Registry.

Patterns of recurrent peritonitis episodes were examined in 6,335 new continuous ambulatory peritoneal dialysis (CAPD) patients entered into the National CAPD Registry. Forty-six percent of all peritonitis episodes were initial occurrences, with 8% of the patients reporting four or more episodes. The proportion of gram-positive and gram-negative infections was constant across episodes. In patients with multiple infections, negative organisms were found to have increased risk of recurring as gram-negative infection. A similar observation was made for fungal infections. Of patients with multiple peritonitis episodes, more than 40% of those who transferred to other maintenance renal replacement therapy identified peritonitis as the reason for transfer. A discrete time logistic model was used to estimate peritonitis risk in 4-month follow-up periods. Patients like those on the registry are estimated to have a 22% risk of developing peritonitis during any 4-month period. This risk was increased 4% for patients aged less than 21 years, 7% for nonwhite patients, and 19% in the period following a peritoneal infection.

Adult↗

Current concepts. Continuous ambulatory peritoneal dialysis.

As a long-term dialysis therapy, CAPD has attractive features for use in children (in whom access to the circulation and immobility are often problems), adults in whom blood access is difficult, patients with diabetes, patients prone to hypotension, and patients seeking independence from a machine or medical facility. CAPD and related procedures are still evolving and improving. Efforts to reduce the rates of peritonitis are ongoing and should decrease the rates of treatment dropout and increase the use of this alternative method of dialysis. Continued research toward improvements in catheter configuration and connection devices and the tailoring of technique to meet the particular needs of patients have made peritoneal dialysis an acceptable replacement therapy in patients with end-stage renal disease. Neither peritoneal dialysis nor hemodialysis is the superior long-term dialysis therapy for all patients; the choice depends on numerous medical, social, geographic, and life-style considerations.

Child↗

Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience.

The Gastrointestinal Tumor Study Group (GITSG) protocol GI-7175 randomized 227 patients between 1975 and 1980 following complete surgical resection of stages B2 and C rectal adenocarcinoma to four treatment arms: (1) no adjuvant therapy, (2) chemotherapy only, (3) radiotherapy only, and (4) radiotherapy and chemotherapy (combined modality). The results of the study showed an advantage for combined modality treatment over no adjuvant therapy for time to recurrence (p = 0.005) and for survival (p = 0.01). Severe acute toxicity was frequent in the combined modality arm (61%) but late effects, including radiation enteritis, have been infrequent. We conclude that postoperative adjuvant therapy is indicated in certain stages of rectal carcinoma and that the present state of knowledge suggests combined modality therapy.

Adenocarcinoma↗

Value of a routine follow-up endoscopy program for the detection of recurrent colorectal carcinoma.

Four hundred fifty-two patients with surgically resected colon or rectal cancer were evaluated to determine the incidence of intraluminal recurrences and the utility of a routine endoscopy screening program for detecting such recurrences. At the time of analysis, recurrent disease was found in 86 of 380 colon cancer patients and 21 of 72 rectal cancer patients. Local recurrence, defined as tumor within 400 cm2 of the primary, was present in 38 of 86 colon, and 11 of 21 rectal cancer patients. Of those 49 local recurrences, 15 were intraluminal, 6 of which were initially detected by a follow-up endoscopy program. Time to diagnosis, stage of disease, and survival were similar for patients whose lesions were detected by routine endoscopy versus those found by other means. New primary (metachronous) lesions defined as an intraluminal lesion occurring at least 5 cm beyond the surgical anastomosis were identified in six colon cancer patients and no rectal cancer patients. Of these six lesions, four were discovered during routine endoscopy. Thus, a routine follow-up endoscopy program is an important tool for the detection of intraluminal recurrence of colon and rectal cancer in patients who have undergone curative resection. However, routine follow-up endoscopy should not be the sole method of follow-up, since the incidence of intraluminal recurrence is small, and may initially be detected by other means in the majority of cases.

Adenocarcinoma↗

Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum.

The Gastrointestinal Tumor Study Group's (GITSG) adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

Adenocarcinoma↗

A survey of the NIH CAPD Registry population with end-stage renal disease attributed to diabetic nephropathy.

A survey of CAPD/CCPD patients with end-stage renal disease attributed to diabetes mellitus done by the USA NIH CAPD Registry obtained information from 499 patients. These data suggest that in diabetics with renal insufficiency, the time interval from age at diagnosis of diabetes to initiation of dialysis decreases as the age of diagnosis increases. Mean interval from the time of diabetes diagnosis to CAPD or CCPD initiation was 25 years for patients less than 20 years of age at diagnosis and 17 years for patients greater than or equal to 30 years of age. This trend is independent of the type of diabetes management and appeared to be independent of the type of diabetes. Patients were categorized on the basis of pre- and post-CAPD management of hyperglycemia. There were several associations noted between type of diabetes therapy and clinical findings: A higher proportion of legally blind patients had used insulin only (33%) compared with patients never using insulin (10%) and 78% of patients using insulin only were white compared with 49% among the never on insulin group. This latter result indicates that race influences the type of diabetes and/or progression of diabetes to renal insufficiency. Patients on insulin only reported parents and/or siblings with diabetes less often than did patients using insulin and oral agents, some insulin, or never any insulin to manage their diabetes. The authors also noted that peritonitis rates were not increased in those patients who added insulin to dialysis solutions.

Adult↗

The 1987 USA National CAPD Registry report.

The National CAPD Registry has noted encouraging trends in CAPD therapy in the U.S. Recently, trained patients have reported lower peritonitis rates, fewer days hospitalized for dialysis-related events, and lower probability of developing a first episode of a complication. If accumulating experience, better patient selection, and new technologic developments further these trends, then the relatively high transfer rates should begin to decrease since many transfers are related to peritonitis and other complications. The Registry's observations suggest that CAPD is an evolving therapy and that as complication rates and transfer rates decrease, CAPD may play an even greater role in the treatment of patients with end-stage renal disease.

Female↗