Giant actin inclusions in hematopoietic cells associated with transfusion-dependent anemia and grey skin discoloration

We evaluated a 13-month-old boy with cytoplasmic inclusions in hematopoietic cells, transfusion-dependent anemia, splenomegaly, and striking grey skin discoloration. Bright blue inclusions, 1 to 5 microns in diameter, were observed, primarily in the cytoplasm, of 30% to 40% of myeloid cells and in occasional monocytes, megakaryocytes, and lymphocytes on Wright Giemsa-stained bone marrow and blood smears. They occasionally involved the nucleus. The inclusions lacked lysosomes, polysaccharides, or lipids. Ultrastructurally, they lacked limiting membranes and consisted of tightly packed microfilaments averaging 7 nm in diameter, consistent with the size of actin monofilaments. On light microscopy, the inclusions stained with a monoclonal antibody to muscle-specific actin. Inclusion-positive cells contained increased F-actin content and were defective in chemotactic factor-activated actin polymerization; inclusion-negative cells polymerized actin normally. Neutrophil and platelet numbers and functional studies were mildly abnormal. Anemia and skin discoloration resolved spontaneously after 18 months, but the giant inclusions have persisted to the present. We conclude that this child has a previously unreported constellation of clinical and laboratory findings comprising severe anemia, intermittent neutropenia and thrombocytopenia, abnormal neutrophil migration and platelet aggregation, giant inclusions of actin in hematopoietic cells, and grey skin discoloration.     

The incidence of painful crisis in homozygous sickle cell disease: correlation with red cell deformability

To determine whether the vasoocclusive severity of homozygous sickle cell (SS) disease is influenced by cellular dehydration, we correlated the incidence of painful crisis with steady-state measurements of red cell hydration. Sixteen children with SS disease were followed for 3.3 to 8 years (mean, 6.8 years), and a single crisis rate was calculated for each patient. At the time of well visits, cellular hydration was assessed by measuring cell deformability, the percentage of red cells with a density greater than or equal to 1.1056 g/mL, and the percentage of irreversibly sickled cells (ISC). The incidence of painful crisis showed a strong positive correlation with Omax, a deformability measurement reflecting cellular hydration (r = .84, P less than .002), and with hemoglobin concentration (r = .59, P = .04). That is, higher crisis rates were observed in patients with less dehydrated, more deformable red cells and also in patients with higher hemoglobin concentrations. Furthermore, cell deformability and hemoglobin concentration were independent predictors of the incidence of painful crisis, which is consistent with separate effects of these two red cells parameters on vasoocclusive severity.     

Phase II study of ifosfamide and etoposide chemotherapy for extensive-disease small-cell lung cancer

We conducted a phase II study of ifosfamide and etoposide chemotherapy in patients with untreated extensive-disease small-cell lung cancer to assess response and toxicity. Between January 1994 and December 1995, 16 patients were treated. Ifosfamide and etoposide doses were ifosfamide 2 g/m2, with mesna, i.v. infusion over 30 minutes on days 1-3 and etoposide 80 mg/m2 i.v. over 120 minutes on days 1-3 every 4 weeks for up to six cycles. All patients were evaluable for toxicity profile and treatment response. As expected, the major toxicity was myelosuppression. With one exception, grade 3 or 4 leukopenia occurred in all patients during treatment, and 48.7% of the total courses had grade 3 or 4 leukopenia. Nine of 16 patients (56.3%) experienced episodes of febrile neutropenia. One toxic death due to febrile neutropenia with sepsis was documented. Toxicities other than leukopenia were few and mild in severity. After two cycles of treatment, the overall response rate was 81.3% (95% confidence interval 62.2-100) in this study. The median duration of response was 8 months and median survival was 11 months. In conclusion, ifosfamide and etoposide is an active combination regimen with acceptable toxicity profile in Chinese patients with extensive-disease small-cell lung cancer.      

A Mobile Phone Integrated Health Care Delivery System of Medical Images

With the growing computing capability of mobile phones, a handy mobile controller is developed for accessing the picture archiving and communication system (PACS) to enhance image management for clinicians with nearly no restriction in time and location using various wireless communication modes. The PACS is an integrated system for the distribution and archival of medical images that are acquired by different imaging modalities such as CT (computed tomography) scanners, CR (computed radiography) units, DR (digital radiography) units, US (ultrasonography) scanners, and MR (magnetic resonance) scanners. The mobile controller allows image management of the PACS including display, worklisting, query and retrieval of medical images in DICOM format. In this mobile system, a server program is developed in a PACS Web server which serves as an interface for client programs in the mobile phone and the enterprise PACS for image distribution in hospitals. The application processing is performed on the server side to reduce computational loading in the mobile device. The communication method of mobile phones can be adapted to multiple wireless environments in Hong Kong. This allows greater feasibility to accommodate the rapidly changing communication technology. No complicated computer hardware or software is necessary. Using a mobile phone embedded with the mobile controller client program, this system would serve as a tool for heath care and medical professionals to improve the efficiency of the health care services by speedy delivery of image information. This is particularly important in case of urgent consultation, and it allows health care workers better use of the time for patient care.     

The human corpus luteum: reduction in macrophages during simulated maternal recognition of pregnancy

It has been shown that immune cells, particularly macrophages, accumulate in the corpus luteum during luteolysis. This study aimed to investigate the effect of maternal recognition of pregnancy on the localization and numbers of macrophages in the human corpus luteum. Corpora lutea (n = 12) were obtained from normally cycling women at the time of hysterectomy and were dated on the basis of serial urinary luteinizing hormone (LH) estimation. In addition, corpora lutea (n = 4) were collected from women who had received daily doubling doses of human chorionic gonadotrophin (HCG) to mimic the hormonal changes of early pregnancy. Macrophages were localized by immunohistochemistry using an anti-CD68 antibody. Steroidogenic cells, steroidogenic cells of thecal origin and endothelial cells were identified on serial sections by immunohistochemistry for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase and von Willebrand factor, respectively. The luteal cells capable of responding directly to HCG were identified by isotopic in-situ hybridization for messenger RNA encoding LH/HCG receptors. Macrophages were localized primarily to the vascular connective tissue and theca-lutein areas of the corpus luteum, although some were found in the granulosa-lutein cell layer. Macrophage numbers increased throughout the luteal phase to a maximum in the late- luteal phase (P < 0.05). Luteal 'rescue' with HCG was associated with a marked reduction in the numbers of tissue macrophages when compared with those of the late-luteal phase (P < 0.001). One of the effects of HCG during maternal recognition of pregnancy is to prevent the normal influx of macrophages into the corpus luteum. As LH/HCG receptors localized to the steroidogenic cells, this implies a fundamental role for steroidogenic cell products in the control of macrophage influx into the human corpus luteum.      

PATIENT SATISFACTION WITH RIZATRIPTAN VERSUS OTHER TRIPTANS: DIRECT HEAD-TO-HEAD COMPARISONS

This study summarises the impact of treatment with rizatriptan 10 mg versus other 5-HT_1B/1D receptor agonists (triptans) on patient satisfaction with medication. Rizatriptan is a potent, selective 5-HT_1B/1D receptor agonist shown to be fast, effective and well tolerated in the acute treatment of migraine. We investigated patients' overall satisfaction with treatment in studies in which direct comparisons with other triptans were made. Data from five double-blind, placebo-controlled trials in which rizatriptan 10 mg was compared with another triptan were included in the analysis. Rizatriptan 10 mg was compared with sumatriptan 100 mg in one parallel study (n=916), sumatriptan 50 mg in two crossover studies (n=1599), naratriptan 2.5 mg in one parallel study (n=502), and zolmitriptan 2.5 mg in one parallel study (n=701). Satisfaction was reported by patients on a seven-point scale ranging from ‘completely satisfied, couldn't be better’ to ‘completely dissatisfied, couldn't be worse’ at 2 hours after dosing. The percent of patients in the top two ‘satisfied’ categories (completely or very satisfied) were analysed. More patients on rizatriptan 10 mg were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p<0.05), sumatriptan 50 mg (40% vs 35%, p<0.05), naratriptan 2.5 mg (33% vs 19%, p<0.01), and zolmitriptan 2.5 mg (38% vs 30%, p<0.05). In all five studies more patients treated with rizatriptan 10 mg or other triptans were completely or very satisfied with treatment than patients receiving placebo (p<0.001, except naratriptan vs placebo p=0.004). The results, combined with the superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg, should enhance the treatment of migraine headache and lead to improved therapeutic intervention in clinical practice.