This month at the NIH NIDDK progenitor cell genome anatomy projects

Readers are encouraged to write letters to the editor concerning articles that have been published in Gastroenterology. Short, general comments are also considered, but use of the Correspondence section for publication of original data in preliminary form is not encouraged. Letters should be typewritten double-spaced and submitted in triplicate.     

NIH conference. Cystinosis: progress in a prototypic disease

OBJECTIVE: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. DESIGN: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. SETTING: University centers in the United States and Canada. PATIENTS: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. INTERVENTION: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. MEASUREMENTS AND MAIN RESULTS: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. CONCLUSIONS: Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.     

NIH conference. Respiratory disease in the immunosuppressed patient.

Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk.     

NIH conference. Recent advances in chronic granulomatous disease

Chronic granulomatous disease represents a group of disorders of phagocytic cell oxidative metabolism involving recurrent infections with catalase-positive microorganisms and chronic inflammation. Genetic heterogeneity and phagocyte abnormalities, including enzyme deficiencies, abnormal elicited membrane potential changes, abnormal acidification of the phagocytic vacuole, and deficiencies of an electron transport cascade, have been associated with its pathogenesis. In addition, recently we have shown abnormal neutrophil C3b-receptor expression, antibody-dependent cellular cytotoxicity, and abnormal microtubule metabolism (tyrosinolation of the alpha-chain of tubulin). Fourteen patients with the disease who were followed at the National Institutes of Health had life-threatening infections, on average, once every 9.6 months. In most of the 119 febrile episodes seen in these patients, no infectious agent was found. Retrospective studies indicated that prophylactic antibiotic therapy, particularly with trimethoprim-sulfamethoxazole, significantly prolonged disease-free intervals to greater than 40 months (p less than 0.05). In serious, life-threatening infections, leukocyte transfusions have been used in therapy. Transfused leukocytes localize and persist at infectious sites, and the clinical efficacy of leukocyte transfusions has been suggested.