Cryoglobulinemia and hepatatrophic viruses.
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Biomarkers↗
Biomedical subjects
A L Baker
Publications and source records attributed to A L Baker.
Prior esophageal variceal bleeding does not adversely affect survival after orthotopic liver transplantation.
Prior variceal bleeding may adversely affect the prognosis of orthotopic liver transplantation. We studied this question by evaluating all 175 adult patients undergoing orthotopic liver transplantation at our institution to determine risk factors associated with mortality after transplantation. Seventy patients demonstrated prior variceal bleeding, and of those, 32 had a course of sclerotherapy. Thirteen also had portal systemic shunts. Compared with the 105 transplant patients who had no prior bleeding, patients who bled were more likely to have parenchymal liver disease (74% vs. 50%), equally likely to have cholestatic liver disease (19%), and less likely to have malignancy (6% vs. 19%) or fulminant liver failure (1% vs. 12%). Bleeding patients also were more likely to be Child-Pugh class C (46% vs. 35%). By the common closing date of December 31, 1990, 26 patients (37%) with prior bleeding and 48 patients (46%) without bleeding died after transplantation. From survival curves, patients with prior bleeding had improved survival rates at 1 yr (65% vs. 54%), at 3 yr (60% vs. 47%) and at 5 yr (55% vs. 43%), although the differences were not statistically significant. With a proportional hazards model to adjust for confounding effects, the relative risk of mortality among patients with prior bleeding was 0.60 (95% confidence interval, 0.27 to 1.30). Sclerotherapy or portal systemic shunts did not alter survival. Important adverse risk factors for mortality included older age at transplantation, black race, malignant disease and more advanced Child-Pugh class. This study suggests that prior esophageal variceal bleeding did not adversely affect the mortality of patients undergoing orthotopic liver transplantation.
Adult↗
Niacin treatment of hypercholesterolemia in children.
OBJECTIVE: To determine the efficacy and adverse effects of niacin treatment of hypercholesterolemia in children. DESIGN: Retrospective review. SETTING: Two university hospital referral clinics. PATIENTS: All children who received single-drug niacin treatment for severe hypercholesterolemia between 1980 and 1991. RESULTS: Twenty-one children, aged 4 to 14 years, were treated with niacin, 500 to 2250 mg daily. Pretreatment total serum cholesterol value (mean +/- SD) was 7.84 +/- 1.14 mmol/L (303 +/- 44 mg/dL), and low-density lipoprotein cholesterol value was 6.28 +/- 1.16 mmol/L (243 +/- 45 mg/dL). Niacin treatment in daily doses > 1000 mg reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30% (P < .001) but had no effect on high-density lipoprotein cholesterol and triglycerides. As in adults, reversible adverse effects were common, occurring in 16 (76%) of the 21 children. Six children (29%) had reversible dose-related elevations of serum aminotransferase levels. Niacin therapy was discontinued in 8 children (38%) because of flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels. CONCLUSIONS: This study suggests that although niacin treatment in children is efficacious, adverse effects are common. Until further study demonstrates long-term safety, niacin treatment should be reserved for the closely-supervised treatment of severe hypercholesterolemia by a lipid specialist.
Adolescent↗
Audiologic profiles of children with Kawasaki disease.
Kawasaki disease (KD) is an idiopathic vasculitis associated with systemic inflammation and profound immunoregulatory changes. Recent reports from Japan and the United States have documented the association of sensorineural hearing loss (SNHL) with acute KD. To further characterize the nature and prevalence of this complication, we prospectively evaluated the hearing of 40 consecutive patients with acute KD at a single institution. Standard audiometric procedures were used, including visual reinforcement audiometry and play audiometry. Auditory brainstem response (ABR) testing using clicks and tone pips (1000-4000 Hz) was performed in patients with abnormal or unreliable results on behavioral audiometry. Acoustic immittance measurements were obtained on all patients. Of the 23 males and 17 females (mean age 3.2 +/- 2.3 years, range 0.6-11.1 years), all but three were evaluated and treated with aspirin and intravenous gama globulin within 1 month of onset of fever. Seven children had test results suggesting sensorineural threshold shifts, 16 had normal hearing, and 14 had inconclusive hearing evaluations. Laboratory data in patients with hearing threshold shifts revealed significantly longer duration of fever (4.1 +/- 1.0 versus 1.9 +/- 0.5 days), and a tendency for higher temperatures and white blood cell counts at diagnosis compared to those with normal hearing. Results suggest that transient as well as persistent SNHL may be associated with the acute vasculitis of KD, and may be associated with laboratory markers indicating more severe systemic inflammation. Audiologic screening should be considered for all patients following KD.
Aspirin↗
Evaluation of patients for liver transplantation.
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Contraindications↗
Growth in adulthood after liver transplantation for glycogen storage disease type I.
Continuation of linear growth late into the third decade of life is rarely observed. This report describes a 27-year-old man with delayed growth and sexual maturation secondary to glycogen storage disease type I who grew 5.3 cm after orthotopic liver transplantation. Sequential improvement in selected measures of metabolic control (blood glucose, lactate, and bicarbonate concentrations) and growth-promoting peptides (testosterone and insulinlike growth factor I) were documented after transplantation and before the increase in height. Potential increases in final stature may be present in adult patients with underlying metabolic disease and delayed skeletal maturation.
Adult↗
OKT3 therapy for hepatic allograft rejection. Differential response in adults and children.
The clinical courses following OKT3 therapy for hepatic allograft rejection (HAR) in adults and children have not been individually defined. We have reviewed our experience with OKT3 therapy for HAR in adults and children to compare: (1) the initial response to OKT3 therapy, (2) the clinical course following OKT3 therapy, and (3) the antimurine antibody response and immunologic monitoring results. Children required OKT3 therapy more frequently than adults: fourteen courses of OKT3 therapy were required in 130 orthotopic liver transplants (OLT) in 108 adult patients, whereas nineteen courses of OKT3 therapy were required in 94 OLT in 78 children (P less than 0.02). Repeat OKT3 therapy was not required in adults--however, four of nineteen courses of OKT3 therapy in children were repeat OKT3 therapy for rejection. No differences existed between adult and pediatric treatment groups with respect to number of prior OLT procedures, previous graft loss to rejection, percentage of ABO-incompatible grafts, frequency of positive donor-recipient lymphocyte crossmatches, or time to first rejection. The initial response to OKT3 therapy (rapid reversal, delayed reversal, and failure) was remarkably similar in adults and children. However, nine of 13 (70%) children with clear evidence of response to OKT3 treatment experienced breakthrough rejection or early recurrent rejection, whereas none of 12 adults suffered breakthrough rejection or early recurrent rejection (P less than 0.01). Early recurrent rejection did not correlate with delayed reversal of rejection, early return of CD3+ cells by peripheral blood monitoring, or development of anti-OKT3 antibodies. All 4 courses of OKT3 retreatment in children were successful in reversing rejection, and breakthrough rejection and early recurrent rejection did not occur. Overall graft and patient survival in pediatric patients requiring OKT3 therapy (67% and 73%) was not different from that in adults (71% and 79%). Results obtained in one patient provide the first evidence that successful OKT3 retreatment of HAR can be achieved in the presence of preexisting idiotypic anti-OKT3 antibody. In conclusion, OKT3 therapy for HAR was required more frequently in children than in adults. The clinical outcome following OKT3 therapy for HAR also differs markedly, with early recurrent rejection and breakthrough rejection occurring more frequently in children.
Adult↗
Small-bowel length and the dose of cyclosporine in children after liver transplantation.
Children, particularly infants, require large oral doses of cyclosporine to achieve immunosuppression after liver transplantation. In 53 children who had received liver transplants, we examined the relation of height, weight, residual small-bowel length, and (in 17 children) the terminal plasma clearance rate of cyclosporine to the dose of cyclosporine required to achieve blood levels of 200 ng per milliliter. The required intravenous dose of cyclosporine (expressed as milligrams per day) increased steeply as body size and bowel length increased, whereas the required oral dose declined with increasing bowel length. When expressed as milligrams per square meter of body-surface area per day, the required intravenous dose did not change with body size, but the required oral dose declined with increasing body size. Small-bowel length correlated closely and inversely with the log of the oral dose of cyclosporine (r = -0.77, P = 0.0001). The rate of clearance was also related to the log of the oral dose (r = 0.57, P = 0.017) but was independent of age and size. Multiple regression analyses that included height and weight showed that only small-bowel length and the rate of clearance from plasma were independently related to the required oral dose of cyclosporine. We concluded that the length of the small bowel is the chief determinant of the required dose of orally administered cyclosporine in children after liver transplantation. Children and infants require large oral doses of cyclosporine because of the limited absorptive surface area of their intestines.
Administration, Oral↗
Antitumor activity of L/1C2-4-desacetylvinblastine-3-carboxhydrazide immunoconjugate in xenografts.
The murine IgG3 monoclonal antibody L/1C2 is reactive with a high percentage of human carcinomas and has preferentially strong reactivity with tumors of squamous differentiation. This antibody was tested for antitumor activity in vitro and in xenograft models as a carbohydrate-linked immunoconjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxhydrazide (DAVLBHYD). The conjugate retained good immunoreactivity and was highly active in a cytotoxicity assay. In human tumor nude mouse xenograft studies, L/1C2-DAVLBHYD antitumor activity was superior to that seen with free drug, free antibody, mixtures of free drug and free antibody, or control DAVLBHYD conjugates prepared with non-tumor-binding IgGs. With well-established tumors, potent antitumor activity was observed, including the ability to specifically regress greater than 400-mg tumors to 0 mg. In some cases, apparent long-term cures were effected. In studies using six different human tumor xenografts, the level of potency of L/1C2-DAVLBHYD was related to L/1C2 antigen expression, although the growth rate probably also contributes to the conjugate sensitivity of the tumors.
Animals↗
Hyperviscosity syndrome in a hypercholesterolemic patient with primary biliary cirrhosis.
A 45-yr-old woman with primary biliary cirrhosis, xanthomatosis, and marked hypercholesterolemia developed symptoms of the hyperviscosity syndrome on three separate occasions. On presentation, she had a plasma total cholesterol concentration of 53.40 mM (2065 mg/dl) and a relative serum viscosity of 2.9. Following three courses of plasma exchange in a 5-day period, the total cholesterol level decreased to 6.75 mM (261 mg/dl) and the viscosity to 1.3. The cutaneous xanthomata were markedly diminished 1 wk following plasma exchange. Despite therapy with colestipol (30 g/d), the hyperviscosity syndrome developed 147 days later. This cycle recurred again 137 days after colestipol was discontinued. Serum viscosity and total cholesterol concentration were highly correlated during the postexchange or accumulation phases (R = 0.95, 95% CI: 0.85, 0.98) and during the exchange or interventional phases (R = 0.95, 95% CI: 0.84, 0.99). Serum viscosity was less significantly correlated with total serum protein (R = 0.84; 95% CI: 0.55, 0.95) or with plasma triglyceride (R = 0.63; 95% CI: 0.26, 0.81). There were no significant correlations of red cell mass, plasma fibrinogen levels, or serum bile salts with viscosity. Subfractionation of plasma into lipoprotein classes showed 45% of total cholesterol in the lipoprotein X fraction and a presumptive slow alpha-lipoprotein species. It is postulated that both the hyperviscosity syndrome and rapid resolution of xanthomata in the patient may be attributable to the physiology of her abnormal lipoprotein particles.
Blood Viscosity↗
Application of reduced-size liver transplants as split grafts, auxiliary orthotopic grafts, and living related segmental transplants.
The University of Chicago program in pediatric liver transplantation continues actively to seek innovative surgical solutions to problems related to the management of children with end-stage liver disease. Among the most important problems facing these children is a shortage of donor organs, which results from three factors in addition to the actual supply of pediatric donors: the concentration of pediatric liver disease in the population younger than 2 years; the necessity for a graft that is small enough; and the epidemiology of accidents and other events that lead to organ donation. Transplantation using a liver lobe as a graft overcomes size disparity and shifts the available supply of organs from older donors to younger recipients. This work describes the technical aspects of recent innovations in the use of liver lobes in pediatric transplantation, simple reduced-size liver transplantation (RLT), split-liver transplantation (SLT), orthotopic auxiliary liver grafting (ALT), and transplantation using a living related donor (LRLT), and compares their results. Since November 1986 a total of 61 procedures have been performed in which a liver lobe was used as a graft: 26 RLT; 30 SLT, 25 in children and 5 in adults; 5 LRLT; and 1 ALT. Overall 62% of transplants performed in children have involved using a liver lobe as a graft. The rates of complications are somewhat higher than with whole-liver transplantation, but this may not be entirely the result of the complex procedures. Split liver transplantation is associated with the highest mortality and complication rates. Living related liver transplantation has been associated with complications in donors and recipients, but to date survival is 100%. Orthotopic auxiliary liver transplantation effectively corrected the metabolic defect in one patient with ornithine transcarbamylase deficiency. Overall the various modalities of using graft reduction have resulted in postoperative results similar to those achieved with full-size grafts, while pretransplantation mortality has been limited to less than 2%. Thus the use of grafts as liver lobes accomplishes the goal of reducing global mortality among children with end-stage liver disease, but at the cost of increased surgical complexity and more postoperative complications.
Adult↗
OKT3 therapy for hepatic allograft rejection: comparison of results in adults and children.
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Adrenal Cortex Hormones↗
Urethral leiomyoma in a cat.
A 13-year-old spayed cat was examined because of a suspected lower urinary tract obstruction. After 2 days, a urethral catheter could not be passed, and the cat was euthanatized. At necropsy, a 1.2-cm intramural mass was detected, obstructing the proximal portion of the urethra. Histologic examination of the well-circumscribed mass revealed a urethral leiomyoma.
Animals↗
Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon.
Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance.
Adenocarcinoma↗
Liver transplantation in the management of fulminant hepatic failure.
Liver transplantation is now performed for the treatment of fulminant hepatic failure, but the selection of patients for this procedure has been incompletely described. We used worsening hepatic encephalopathy, clinical evidence of brain edema, and prolongation of the prothrombin time after 24-48 h of intensive medical treatment as key factors influencing the decision to recommend liver transplantation. Thirty-seven patients (29 adult, 8 pediatric) were admitted with fulminant hepatic failure. Ten improved with medical treatment, so liver transplantation was not recommended. Twenty-seven deteriorated despite medical treatment. Eight of these, 7 with grade 4 hepatic encephalopathy and persistent coagulopathy, did not receive transplantation because of contraindications (n = 5), failure to find a donor (n = 1), or refusal of therapy (n = 2). None of these survived. Sixteen of the other 19 patients developed grade 4 hepatic encephalopathy, 5 had brain edema, and all had persistent coagulopathy, so liver transplantation was performed. One year actuarial survival was 58%. This retrospective analysis confirms that survival exceeding 50% can be obtained with liver transplantation in patients with fulminant hepatic failure. Additional studies of prognostic markers are needed to define the role of liver transplantation in the management of this disease.
Adolescent↗
New antitumor monoclonal antibody-vinca conjugates LY203725 and related compounds: design, preparation, and representative in vivo activity.
A method has been developed to allow the direct coupling of the cytotoxic vinca alkaloid 4-desacetylvinblastine-3-carbohydrazide (DAVLB hydrazide) to a variety of murine monoclonal antibodies directed against human solid tumors. Periodate oxidation of carbohydrate residues on the antibodies, followed by reaction with DAVLB hydrazide in aqueous acid affords, in most cases, conjugates with conjugation ratios of 4-6 vincas per antibody in high yield without significantly impairing antigen binding or solubility. The outcome of the conjugation reaction is highly dependent on the concentration of, and time of exposure of the protein to, the oxidant. These conjugates exhibit potent antitumor activity in vivo against a number of human solid tumor-nude mouse xenografts, with efficacy and safety increased over unconjugated DAVLB hydrazide. This antitumor activity is also superior to that of similarly prepared but nontarget tumor binding antibody-DAVLB hydrazide conjugates. MoAb-DAVLB hydrazide conjugates release DAVLB hydrazide in solution in a temperature- and pH-dependent manner. Hydrolytic release of unmodified DAVLB hydrazide from tumor-localized MoAb-DAVLB hydrazide conjugates in vivo may be an important factor in their antitumor activity.
Animals↗
[Shunt surgery with reference to indications for liver transplantation].
Sclerotherapy and protosystemic shunt surgery are established procedures for treating bleeding esophageal varices. Liver transplantation (OLT) has not yet been established as primary therapy of portal hypertension. In a series of 43 patients with uncontrollable bleeding, shunt surgery was employed in 26 patients with contra-indications to OLT and in 2 whose liver disease had not progressed. In the remaining 15 patients, OLT was performed in urgent (n = 8) and emergency settings (n = 7). The results obtained indicate that immediate shunting in nontransplant candidates results in one-year survival for 67-83% of Child's class A or B Patients and only 42% Child's C category regardless of the type of shunt procedure performed. In transplant candidates with a similar risk status (Child's B and C) 5 of 8 patients receiving an urgent transplant and 4 of 7 patients receiving emergency OLT during active bleeding survived for one year or more. These results indicate that bleeding varices can be treated successfully by OLT.
Esophageal and Gastric Varices↗
Chronic hepatitis: disease factors at diagnosis predictive of mortality.
PURPOSE: Chronic hepatitis is known to be a disease with substantial mortality. The purpose of this study was to identify prognostic factors in a large group of patients with chronic hepatitis. We also wanted to determine whether the aminopyrine breath test (ABT) is of additional prognostic value in evaluation of this disease. PATIENTS AND METHODS: We studied 94 patients who had had a biopsy-proven diagnosis and an ABT between June 1, 1977, and June 30, 1981. Clinical features and biochemical test results at the time of diagnosis were retrieved from medical records, and histologic severity was assessed by reviewing all liver biopsy specimens under code. Survival was determined at a mean of 60 months. Data were studied with a Cox proportional hazards model to identify predictors of mortality and to control for confounding variables. RESULTS: Cumulative mortality as of December 31, 1985, was 5 percent in chronic persistent hepatitis, 6 percent in chronic active hepatitis, 29 percent in chronic active hepatitis with bridging necrosis, and 53 percent in chronic active hepatitis with cirrhosis. Histologic severity was a predictor of death (p less than 0.005). Other predictors of mortality were disease caused by hepatitis B virus (p less than 0.005), a high alkaline phosphatase level (p less than 0.025), a low alanine aminotransaminase level (p less than 0.001), and a depressed ABT result (p less than 0.005). CONCLUSION: The results suggest that patients with chronic hepatitis with one or more of these risk factors have an increased mortality and should be followed closely for liver failure, which may necessitate medical therapy or surgical intervention.
Adult↗