Interdisciplinary approach to treat dyskeratosis congenita associated with severe aplastic anemia: A case report

This paper reports on a 4‐year‐old male who had dyskeratosis congenita and who acquired severe aplastic anemia. The patient developed hyperpigmentation of the face, neck and chest region, arms, shoulders and legs. In addition, he had dry skin, deformed fingernails and toenails, sparse hair and eyebrows and hyperkeratosis of the dorsum of the hands and feet. Laboratory and histological analysis revealed severe pancytopenia and dyserythropoiesis of red blood cells, hypocellularity of white blood cells and decreased megakaryocytes with dysplasia. The intraoral examination identified bleeding gums; petechiae of the palate, tongue and cheek mucosa; and an atrophic, smooth and shining dorsal surface of the tongue. There were deep carious lesions in the deciduous mandibular molars and maxillary anterior teeth; as well as mobility of mandibular left canine, which had bone loss. The treatment for oral lesions included diet changes, improved oral hygiene, and extraction of the deciduous teeth destroyed by caries.     

Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Post-natal development modulates the rat seminal vesicle sensitivity to sympathomimetic agonists

Summary The post-natal development-related changes in the sensitivity to sympathomimetic agonists were studied in the seminal vesicle of 40-, 60- and 120-day old rats by determining the pD₂ values for adrenaline, phenylephrine and methoxamine. The age-related changes in the neuronal and extraneuronal uptake of sympathomimetic agonists were also determined.The seminal vesicle sensitivity to adrenaline, phenylephrine and methoxamine increased in sexually mature rats (60- and 120-day old) (concentration-effect curves shifted to the left and pD₂ values increased) when compared with immature rats (40-day old). Cocaine, a neuronal uptake inhibitor, induced supersensitivity to adrenaline at all ages, but did not affect the sensitivity to methoxamine. The ratio between the EC₅₀ values for adrenaline in the presence and in the absence of cocaine was reduced in tissues of mature animals. This reduction suggests a loss of function of the neuronal uptake system with sexual development. In the presence of cocaine the pD₂ value for adrenaline was increased during sexual development. Thus, the age-related changes in the adrenaline sensitivity were observed even when neuronal uptake was not operative, suggesting age-related changes at the post-junctional level, which was confirmed by the increase in the seminal vesicle sensitivity to methoxamine. In the presence of the extraneuronal uptake inhibitor, corticosterone, the sensitivity to adrenaline did not change and the age-related changes persisted.In conclusion, the sexual development-related changes in seminal vesicle sensitivity to sympathomimetic agonists may be due not only to an age-related loss of function of the neuronal uptake system but may also be a consequence of age-related changes at the post-junctional level.Correspondence to C. S. Porto at the above address     

Erythropoietin (Epo), protein and iron supplementation and the prevention of anaemia of prematurity: effects on serum immunoreactive Epo, growth and protein and iron metabolism

The effect of recombinant human (r-Hu) erythropoietin (Epo) (300 IU/kg per week for 4 weeks) was studied in healthy preterm infants ( n = 14) fed human milk with additional milk protein and high doses of iron. The controls ( n = 15) were in themselves a study group and were used to follow the natural course of anaemia of prematurity on such nutrition. Serum immunoreactive Epo (SiEpo) increased significantly 24h after r-HuEpo injections (range 36 to > 128 mU/ml) and remained at these levels throughout the treatment period. r-HuEpo in such moderate doses kept haemoglobin above 11 g/dl. Bodyweight gain, protein and iron parameters indicated adequacy of dietary protein and iron. In controls, siEpo increased during the first weeks after nutritional supplementation, with a concommitant rise in reticulocyte count. At age 3 weeks, despite low siEpo levels, reticulocyte counts indicated active erythropoiesis. Following further moderate increases in siEpo, the reticulocyte count increased to high levels (7%). The reticulocyte response suggests that erythropoiesis in preterm infants is less dependent upon Epo levels than in adults.     

Osteomyelitis in the neonate. Clinical aspects and the role of radiography and scintigraphy in diagnosis and management

Based on experience with 22 cases of neonatal osteomyelitis in 10 years, the authors suggest these patients can be divided into two groups depending on severity of disease. Premature infants requiring umbilical catheterization and severely ill full-term infants constitute a high-risk group; signs are more overt, multifocal infection and joint involvement more frequent, and severe skeletal deformities more common. The patients in the low-risk group had much milder disease but also presented more difficulty in diagnosis because of the vagueness of the presenting signs. Radiographic examination is essential for diagnosis and follow-up of osteomyelitis, particularly limb deformities. Bone scans should be reserved for situations in which the clinical and radiographic findings are equivocal.     

Carpal avascular necrosis: MR imaging

The authors evaluated the use of magnetic resonance (MR) imaging in diagnosis of avascular necrosis (AVN) of carpal bones by examining 21 patients with wrist pain and two healthy volunteers. MR images were compared with conventional radiographs in every case and with bone scintigrams in 18 cases. MR imaging was slightly less sensitive than bone scintigraphy in depicting AVN, but in patients who were imaged with long repetition time (TR)/long echo time (TE) sequences in addition to short TR/short TE sequences, MR imaging was found to be more specific. While the authors believe that bone scintigraphy remains the screening test of choice for patients with wrist pain and normal plain radiographs, MR imaging promises to add significant diagnostic information in cases in which bone scans are abnormal.