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Biomedical subjects

J McCauley

Publications and source records attributed to J McCauley.

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

Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity: multiple sclerosis and primary biliary cirrhosis.

A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet "infant" immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (approximately 50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner.

Artificial Intelligence↗
PubMed1995

The "battering syndrome": prevalence and clinical characteristics of domestic violence in primary care internal medicine practices.

OBJECTIVES: To determine the prevalence of domestic violence among female patients and to identify clinical characteristics that are associated with current domestic violence. DESIGN: Cross-sectional, self-administered, anonymous survey. SETTING: 4 community-based, primary care internal medicine practices. PATIENTS: 1952 female patients of varied age and marital, educational, and economic status who were seen from February to July 1993. MEASUREMENTS: The survey instrument included previously validated questions on physical and sexual abuse, alcohol abuse, and emotional status and questions on demographic characteristics, physical symptoms, use of street drugs and prescribed medications, and medical and psychiatric history. RESULTS: 108 of the 1952 respondents (5.5%) had experienced domestic violence in the year before presentation. Four hundred eighteen (21.4%) had experienced domestic violence sometime in their adult lives, 429 (22.0%) before age 18 years, and 639 (32.7%) as either an adult or child. Compared with women who had not recently experienced domestic violence, currently abused patients were more likely to be younger than 35 years of age (prevalence ratio [PR], 4.1 [95% CI, 2.8 to 6.0]); were more likely to be single, separated, or divorced (PR, 2.5 [CI, 1.7 to 3.6]); were more likely to be receiving medical assistance or to have no insurance (PR, 4.3 [CI, 2.8 to 6.6]); had more physical symptoms (mean, 7.3 +/- 0.38 compared with 4.6 +/- 0.08; P < 0.001); had higher scores on instruments for depression, anxiety, somatization, and interpersonal sensitivity (low self-esteem) (P < 0.001); were more likely to have a partner abusing drugs or alcohol (PR, 6.3 [CI, 4.4 to 9.2]); were more likely to be abusing drugs (PR, 4.4 [CI, 1.9 to 10.4]) or alcohol (PR, 3.1 [CI, 1.5 to 6.5]); and were more likely to have attempted suicide (PR, 4.3 [CI, 2.8 to 6.5]). They visited the emergency department more frequently (PR, 1.7 [CI, 1.2 to 2.5]) but did not have more hospitalizations for psychiatric disorders. In a logistic regression model into which 9 risk factors were entered, the likelihood of current abuse increased with the number of risk factors, from 1.2% when 0 to 1 risk factors were present to 70.4% when 6 to 7 risk factors were present. CONCLUSIONS: In a large, diverse, community-based population of primary care patients, 1 of every 20 women had experienced domestic violence in the previous year; 1 of every 5 had experienced violence in their adult life; and 1 of every 3 had experienced violence as either a child or an adult. Current domestic violence is associated with single or separated status, socioeconomic status, substance abuse, specific psychological symptoms, specific physical symptoms, and the total number of physical symptoms.

Adolescent↗
PubMed1995

A prospective randomized trial of FK506-based immunosuppression after renal transplantation.

A group of 204 adult patients was entered into a prospective, randomized trial comparing FK506/prednisone with FK506/azathioprine/prednisone after renal transplantation between August 1, 1991 and October 11, 1992. The purpose of the study was to see if the addition of azathioprine would reduce the incidence of rejection and improve graft survival. The recipient population was unselected, with 61 (30%) patients undergoing retransplantation, 37 (18%) having a panel-reactive antibody greater than 40%, and 33 (16%) over 60 years of age. The mean recipient age was 43.8 +/- 13.7 years (range 17.6-78). The mean donor age was 34.0 +/- 20.1 years (range 0.3-75); 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hr. Living donors were the source of 13% of the kidneys. The mean follow-up was 22 +/- 4 months (range 12-29). Overall one-year actual patient survival was 94%. Overall one-year actual graft survival was 87%. Patients starting on double therapy had a one-year actual patient survival of 96% and a one-year actual graft survival of 92%. Patients starting on triple therapy had a one-year actual patient survival of 91% (P = ns compared with double therapy), and a one-year actual graft survival of 82% (P < 0.02, compared with double therapy). Overall results with first cadaver transplants included a one-year actual patient survival of 94% and one-year actual graft survival of 88%, with no differences between double and triple therapy. The overall incidence of rejection was 48%, with 54% in the double therapy group and 41% in the triple therapy group (P < .07). The incidence of steroid-resistant rejection requiring antilymphocyte therapy (OKT3 or ATGAM) was 13%, and was not different between the double and triple therapy groups. The mean serum creatinine was 1.8 +/- 0.8 mg/dl. The mean BUN was 33 +/- 21 mg/dl, with no significant difference between the therapy groups. The mean serum cholesterol was 192 +/- 49 mg/dl. A total of 56% of the patients are off prednisone, and 35% of the patients are not taking any antihypertensive medications. Other complications included cytomegalovirus--14%; new-onset diabetes--16% (half of which was reversible); and posttransplant lymphoproliferative disorder--1%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

FK506 in pediatric kidney transplantation--primary and rescue experience.

Between 14 December 1989 and 17 December 1993, 43 patients undergoing kidney transplantation alone at the Children's Hospital of Pittsburgh received FK506 as the primary immunosuppressive agent. The mean recipient age was 10.2 +/- 4.8 years (range 0.7-17.4 years), with 7 (16%) children under 5 years of age and 2 (5%) under 2 years of age. Fifteen (35%) children underwent retransplantation, and 5 (12%) had a panel-reactive antibody level greater than 40%. Twenty-two (51%) transplants were with cadaveric donors and 21 (49%) were with living donors. The mean follow-up was 25 +/- 14 months; there were no deaths; 1- and 3-year actuarial graft survival was 98% and 85%. The mean serum creatinine and blood urea nitrogen were 1.2 +/- 0.6 mg/dl and 26 +/- 11 mg/dl; the calculated creatinine clearance was 75 +/- 23 ml/min per 1.73 m2. Twenty-four (62%) patients have been successfully withdrawn from steroids and 24 (62%) require no anti-hypertensive medication. Improved growth was seen, particularly in pre-adolescent children off steroids. Between 28 July 1990 and 2 December 1993, 24 children were referred for rescue therapy with FK506, 14.6 +/- 16.4 months (range 1.1-53.2 months) after transplantation. Nineteen (79%) were referred because of resistant rejection; 4 (17%) were referred because of proteinuria; 1 (4%) was switched because of steroid-related obesity. There were no deaths; 1- and 2-year graft survival was 75% and 68%; 17 (71%) patients were successfully rescued, including 1 of 2 patients who arrived on dialysis; 4 (24%) of the successfully rescued patients were weaned off steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity.

Hyperlipidemia has been implicated in the pathogenesis of experimental progressive glomerulosclerosis, but its role in human renal injury is controversial. This report describes a 12-yr-old boy presenting with massive proteinuria, hepatomegaly, anemia, severe mixed hyperlipidemia, and progressive renal failure. The initial renal biopsy disclosed large numbers of foam cells that were shown to be monocytes. Evidence is presented suggesting that apoprotein-E2 homozygosity in our patient, together with an 88% reduction in plasma lipoprotein lipase activity associated with severe nephrotic syndrome, is responsible for the atypical clinical features, lipoprotein phenotype III with chylomicronemia, and renal lipidosis. A regimen of dietary lipid restriction, gemfibrozil, and niacin resulted in significant but partial improvement of the dyslipidemia and resolution of the hepatomegaly and ascites. This report stresses the importance of characterizing unique lipid disorders in patients with nephrotic syndrome in order to prescribe effective lipid-lowering strategies. Moreover, the striking resemblance of the clinical and nephrohistologic features of this patient to those occurring in experimental models of coexisting glomerular injury and hyperlipidemia led to the speculation that, in this setting, the hyperlipidemia may contribute to the development of progressive glomerulosclerosis.

Apolipoproteins E↗
PubMed1995

The superiority of tacrolimus in renal transplant recipients -- the Pittsburgh experience.

Tacrolimus is a superior immunosuppressive agent in patients undergoing renal transplantation. In adults, the 1- and 3-year actuarial patient survivals were 95% and 92%, and the 1- and 3-year actuarial graft survivals were 89% and 80%. For first cadaver kidneys, the 1- and 3-year actuarial graft survivals were 91% and 82%, with a projected half-life of 11.9 years. Sixty-nine percent of successfully transplanted patients were weaned off steroids. In pediatric patients, the 1- and 4-year actuarial patient survivals were 100% and 96%, and the 1- and 4-year actuarial graft survivals were 99% and 85%. Seventy-three percent of successfully transplanted children were weaned off steroids. Tacrolimus was also useful as a rescue agent, with an initial success rate of 74%. Tacrolimus has been used successfully in kidney/ pancreas transplantation, with 100% patient, 95% kidney, and 79% pancreas graft survival. Tacrolimus should be considered the immunosuppressive agent of choice in renal transplantation.

Adolescent↗
PubMed1994

FK506 "rescue" for resistant rejection of renal allografts under primary cyclosporine immunosuppression.

Seventy-seven patients with ongoing acute rejection on initial CsA therapy were converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone primary transplantation and 18 had been retransplanted; there were 52 cadaveric and 25 living-donor transplants. The indications for conversion to FK506 were ongoing, biopsy-confirmed rejection in all patients, including vascular rejection in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months) after transplantation. Sixty-one of the 77 patients (79%) had already received one or more courses of an antilymphocyte preparation (OKT3: n = 33; ALG or ATG: n = 1; OKT3+ALG/ATG: n = 27). Of the 77 patients, 57 (74%) have been successfully rescued and still have functioning grafts with a mean follow-up of 14 months, with a mean serum creatinine of 2.35 +/- 0.97 mg/dl. Eighteen patients were already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%) were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the 61 patients previously treated with antilymphocyte preparations, 48 (79%) were rescued. In those salvaged, prednisone doses have been lowered from 22.2 +/- 7.2 mg/day preconversion to 7.5 +/- 5.6 mg/day postconversion, and 12 patients are on FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4 +/- 20.5 mg/dl preconversion and 93.2 +/- 22 postconversion (P = 0.07), uric acid 7.3 +/- 2.3 and 7.1 +/- 1.5 mg/dl (P = 0.53), and triglycerides 199.2 +/- 101.6 and 167.2 +/- 106.4 mg/dl (P = 0.06). Cholesterol levels were significantly lower following FK conversion (207.7 +/- 46.5 mg/dl pre. vs. 188.3 +/- 39.7 post., P = 0.007). FK506 is capable of salvaging renal allografts with ongoing acute rejection on CsA therapy, even when antilymphocyte preparations have been ineffective.

Adolescent↗
PubMed1994

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies.

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (> 10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although performed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed.

Adolescent↗
PubMed1994

A prospective, randomized trial of FK-506 in renal transplantation--a comparison between double- and triple-drug therapy.

Previous clinical evaluation of FK506 in renal transplantation has demonstrated equivalent patient and graft survival when compared with cyclosporine-based regimens. However, lower steroid and anti-hypertensive mediation requirements and lower serum cholesterol levels have been seen in patients receiving FK506. In August, 1991, a prospective, randomized trial was begun, comparing FK506/prednisone with FK506/azathioprine/prednisone. Two-hundred-and-four adults were entered into this trial between August 1, 1991, and October 11, 1992. The mean recipient age was 43.8 +/- 13.7 years, with a range of 17.6-78.0 years. Sixty-one (30%) recipients received a 2nd, 3rd or 4th transplant, while 35 (17%) had a PRA greater than 40% at the time of transplant. Thirty-three (16%) of the transplants were in recipients over 60 years of age, Thirteen percent of the kidneys were from living donors; 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hours, and the mean donor age was 34 +/- 2.10 years, with a range from 4 months to 75 years. With a mean follow-up of 9 +/- 4 months, the 1-year actuarial patient survival is 93%; for the two-drug group it is 95%, and for the three-drug group it is 91% (p = NS). One-year actuarial graft survival is 86%; in the two-drug group it is 90%, while in the three-drug group it is 82% (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗