Persistent nausea and anorexia after marrow transplantation: a prospective study of 78 patients.

BACKGROUND: Persistent nausea, vomiting, anorexia, and poor oral intake are common after hematopoietic cell transplantation. In the past, herpesvirus infections and acute intestinal graft-versus-host disease (GVHD) were the most common causes. METHODS: We studied 76 patients with 78 episodes of these symptoms to discern the causes. Diagnoses were based on histology of skin and intestinal biopsy specimens, viral cultures, and responses to therapy. RESULTS: The mean day of study entry was day 57+/-31.3 posttransplant. Acute GVHD was the most common cause of symptoms, affecting 63 patients (81%) as the sole cause of symptoms and an additional 4 patients (5%) who had other concurrent causes. Patients with GVHD had marrow donors who were unrelated or HLA-mismatched in 27/63 cases. Gastric edema, erythema, and apoptotic epithelial cells were the most useful findings for the diagnosis of GVHD. Prednisone therapy (1-2 mg/kg/day) was effective in 58 of 63 patients (92%). Infection by herpes simplex virus, cytomegalovirus, or Candida was found in six patients, three of whom had concurrent GVHD. Other causes of symptoms were medications (one patients), parenteral nutrition (one patient), and sagittal sinus thrombosis (one patient). CONCLUSIONS: Acute GVHD is now the dominant cause of persistent nausea and anorexia in marrow transplant patients who are beyond day 20 posttransplant. The diagnosis can be made clinically in most cases and confirmed by endoscopic biopsy of gastric mucosa. Infections, medications, and rare cases of central nervous system disease are much less common.

Oral beclomethasone dipropionate for treatment of human intestinal graft-versus-host disease.

Intestinal graft-versus-host disease (GVHD) causes anorexia, vomiting, abdominal pain, and diarrhea. We investigated oral beclomethasone dipropionate (BDP), a potent, topically active corticosteroid, as therapy for this disease. Forty-two allogeneic marrow-graft recipients with biopsy-proven intestinal graft-versus-host disease of mild-to-moderate severity received BDP (8 mg daily) for up to 28 days. Weekly symptom scores, oral intake, and surveillance throat and stool cultures were compared with baseline values. Adrenal testing was performed serially in patients not receiving concurrent prednisone. Improvement was seen in appetite (P < 0.001), oral intake (P < 0.001), nausea (P = 0.013), and diarrhea (P = 0.02) over the course of therapy, and an overall beneficial response was observed in 72% of 40 evaluable patients. Surveillance cultures of throat and stool showed no increase in bacterial or fungal colonization over time. The adrenal axis became suppressed in 11 of 20 evaluable patients (55%) but suppression was not a prerequisite for clinical response, as 6 of 9 patients who retained normal adrenal function improved clinically. We conclude that oral BDP is a safe and effective treatment for mild-to-moderate intestinal graft-versus-host disease. Systemic absorption probably occurs, but adrenal suppression is not a prerequisite for clinical efficacy, suggesting that the biological effect is primarily topical. BDP should be further investigated as a topical therapy for intestinal GVHD.

Rapid DNA fragmentation from hypoxia along the thick ascending limb of rat kidneys.

Extensive DNA fragmentation, a marker for programmed cell death, was selectively and rapidly induced by hypoxia in the thick ascending limbs of rat kidneys. In isolated perfused kidneys, DNA breaks were present in medullary tubules as early as after 10 minutes of local hypoxia and were prevented by reduction of metabolic work. In a model of radiocontrast-induced acute renal failure, DNA breaks were detected selectively along thick ascending limbs as early as 15 minutes following insult, preceding overt morphological damage. Hypoxia induces rapid DNA fragmentation along thick ascending limbs, where programmed cell death could play an important role in nephron injury and kidney failure.

Esophageal infections: risk factors, presentation, diagnosis, and treatment.

Infections of the esophagus are unusual in the general population and strongly imply immunodeficiency, although immunocompetent individuals are not exempt. HIV infection is predominant among risk factors for infectious esophagitis. For all immunocompromised patients, the most frequently identified esophageal pathogens are Candida, CMV, and HSV. Peculiar to HIV-infected patients are idiopathic esophageal ulcers as well as unusual bacteria and parasites. Patterns of presentation differ with each infecting organism, and clinical features should be used as a guide in achieving a correct diagnosis. For example, a patient with AIDS presenting with esophageal symptoms and thrush, along with abdominal pain, nausea, vomiting, and fever, is unlikely to resolve all symptoms with empiric antifungal therapy alone. Parsimony of diagnosis does not hold among immunodeficient patients in whom concurrent infections are common. Accurate and timely diagnoses are essential as effective treatments are available for particular etiologies. Finally, among immunocompromised patients, all esophageal symptoms are not necessarily due to an infection, and possible diagnoses of pill esophagitis, acid-peptic injury, or structural and functional abnormalities should not be overlooked.

An evaluation of antioxidant effects on recovery from postischemic acute renal failure.

Xanthine oxidase (XO) activity and hydroxyl radical (.OH) formation are widely proposed mediators of renal reperfusion injury, potentially altering the severity of, and recovery from, postischemic acute renal failure. The goal of this study was to ascertain whether combination XO inhibitor (oxypurinol) and .OH scavenger (Na benzoate) therapy, given at the time of renal ischemia, alters the extent of: (1) tubular necrosis and filtration failure; (2) DNA fragmentation/apoptosis (assessed in situ by terminal deoxynucleotidyl transferase reactivity); (3) early tubular regenerative responses (proliferating cell nuclear antigen expression; (3H)thymidine incorporation); and (4) the rate and/or degree of functional and morphologic repair. The effects of XO inhibition, .OH scavengers, and "catalytic" iron (FeSO4) on human proximal tubular cell proliferation in vitro were also assessed with a newly established cell line (HK-2). Male Sprague-Dawley rats were subjected to 35 min of bilateral renal arterial occlusion with or without oxypurinol/benzoate therapy. These agents did not alter the extent of tubular necrosis or filtration failure, proliferating cell nuclear antigen expression or thymidine incorporation, or the rate/extent of renal functional/morphologic repair. DNA fragmentation did not precede tubular necrosis, and it was unaffected by antioxidant therapy. By 5 days postischemia, both treatment groups demonstrated regenerating epithelial fronds that protruded into the lumina. These structures contained terminal deoxynucleotidyl transferase-reactive, but morphologically intact, cells, suggesting the presence of apoptosis. Oxypurinol and .OH scavengers (benzoate; dimethylthiourea) suppressed in vitro tubular cell proliferation; conversely, catalytic Fe had a growth-stimulatory effect. These results suggest that: (1) XO inhibition/.OH scavenger therapy has no discernible net effect on postischemic acute renal failure; (2) DNA fragmentation does not precede tubular necrosis, suggesting that it is not a primary mediator of ischemic cell death; and (3) antioxidants can be antiproliferative for human tubular cells, possibly mitigating their potential beneficial effects.