The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit

Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Limited joint mobility in Sri Lankan patients with non-insulin- dependent diabetes

Two hundred and sixteen patients with non-insulin-dependent diabetes (NIDDM) and 216 age- and gender-matched controls were studied to assess the prevalence of limited joint mobility (LJM). Joint mobility was measured by goniometry at metacarpophalangeal and subtalar joints, and those in whom a prayer sign was elicited were said to have cheiroarthropathy. Forty diabetic patients and 10 controls had cheirorathropathy. The mean range of motion was reduced at metacarpophalangeal joints in diabetic patients with cheiroarthropathy (36.8 +/- 9.2) and without cheiroarthropathy (45.7 +/- 8.1) when compared to controls (51.4 +/- 9, P < 0.01). Mobility at subtalar joints was reduced in those with cheiroarthropathy (25 +/- 5.3, P < 0.01) when compared to controls (32.4 +/- 4.1) and diabetic patients without cheiroarthropathy (27.4 +/- 4.6). No differences in subtalar mobility existed between diabetic patients without cheiroarthropathy and controls. Significant differences were observed in the presence of foot ulceration (35 vs 16%) in those with and without cheiroarthropathy. We conclude that cheiroarthropathy is seen in Sri Lankan patients with NIDDM and that significant limitation of joint mobility is present in patients with NIDDM who do not have overt cheiroarthropathy and that overt cheiroarthropathy may be a marker for a high risk of foot ulceration.      

胃癌病因:人N-亚硝酰胺暴露

胃癌死亡率居我国恶性肿瘤之首.其危险因素包括:①化学因素,如胃内合成的亚硝基化合物(NOC)和高盐饮食;②生物因素,如幽门螺杆菌感染和摄入生物毒素;③营养因素,如维生素C、硒和其他抗氧化剂等缺乏.NOC的胺类前体物和亚硝化剂(亚硝酸根和各种氧化氮)广泛存在于人体内外环境中,研究发现NOC暴露,可能与上消化道肿瘤的发生有关.高盐饮食和某些微量营养素缺乏,则能够增强NOC的致癌性.幽门螺杆菌感染与胃腺癌发生的关系尚未确定,但与胃粘膜相关性淋巴样组织淋巴瘤(MALT)的存在关系密切,机制不明.已知感染该菌能引发萎缩性胃炎和胃酸缺乏,间接促进NOC胃内合成.可见,NOC是多种胃癌高危因素的作用靶点,是证据最多的诱发胃癌因素.     

Acute respiratory failure that complicates the resuscitation of pediatric patients with scald injuries.

Respiratory failure that requires endotracheal intubation is an uncommon but potentially fatal complication of scald burns in children. Because scalds are rarely associated with a direct pulmonary injury, the pathophysiology of respiratory failure is unclear. A possible mechanism may be upper airway edema, diminished pulmonary compliance secondary to fluid resuscitation, or both. To identify an at-risk population for intubation after a scald injury, the hospital courses of 174 consecutive patients under the age of 14 years who were admitted after a scald injury to a single burn center during a 6-year period were examined. Seven of these patients (4%) required endotracheal intubation. No patient older than 2.8 years or who had a scald injury that covered less than 19% of the total body surface area required intubation. Patients who required intubation were younger (mean age, 1.4 vs. 2.8 years, P<.001), had a larger mean burn size (29.9% vs. 12.3% total body surface area, P<.001), and required more fluid resuscitation (7.66 vs. 4.07 cc/kg per percentage of total body surface area burned, P<.001) than patients who did not require intubation. Examination of the adequacy of resuscitation revealed that the intubated patients had an average hourly urine output of 0.84 cc/kg during the first 24 hours, suggesting that resuscitation was not excessive. Multivariate analysis demonstrated that both larger burn size (P = .041) and younger age (P = .049) were independent predictors of the need for intubation. Young patients with large body surface area burns that required large volumes of resuscitation comprise an at-risk group for respiratory failure after a scald injury. Increased vigilance is merited during the resuscitation of these patients.     

Accuracy of dual-energy radiographic absorptiometry of the lumbar spine: cadaver study

Dual-energy radiographic absorptiometry (DRA) was used to measure the bone mineral content and area density of lumbar vertebrae (L2-L3) in 11 cadavers. These data were subsequently compared with measured ash content and density. Excellent correlation was obtained between bone mineral content measured with DRA and ash weight (r = .963, P less than .0001). The accuracy error in determining mineral content in lumbar vertebrae with DRA was about 9%. In addition, strong correlation was observed between bone mineral density measured with DRA and ash density (r = .881, P less than .0001).     

Meniscal abnormalities: prospective correlation of double-contrast arthrography and arthroscopy

In a prospective study conducted over a 12-month period, 30 patients underwent double-contrast arthrography of the knee followed by arthroscopic study. An 80% correlation rate was found between results. Arthrography had a higher rate of accuracy (93%) than arthroscopy (84%) and had a 7% false-positive and 0% false-negative rate. A commonly overlooked arthrographic sign--the triple-S or stuck sail sign--was 91% accurate in the prediction of meniscal tears. The complementary nature of the two examinations is discussed.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes

This report describes the production and characterization of 13 rodent monoclonal antibodies to the human erythrocyte anion transport protein AE1 (syn. band 3). Eleven antibodies (4 murine and 7 rat) recognize epitopes dependent on the integrity of the third extracellular loop of the protein. Two antibodies (1 murine and 1 rat) recognize epitopes on the N-terminal cytoplasmic domain. Quantitative binding studies using radioiodinated IgG and Fab fragments of antibodies to extracellular epitopes on AE1 ranged from 77,000 to 313,000 (IgG) and from 241,000 to 772,000 (Fab) molecules bound at saturation. The results indicate that the epitopes recognized by different antibodies vary in their accessibility and suggest that there is heterogeneity in the organization of individual AE1 molecules in the red blood cell membrane. Quantitative binding studies on South East Asian ovalocytes using several antibodies to AE1 and an anti-Wrb show a marked reduction in the number of antibody molecules bound at saturation. These results are consistent with the existence of highly cooperative interactions between transmembrane domains of AE1 in normal erythrocytes and the disruption of these interactions in the variant AE1 found in South East Asian ovalocytes.     

P21 Design and operation of a human breath freshness panel

Objective  Practical treatment of halitosis requires tongue cleaning since volatile sulphur compounds (VSC) seems mainly to be from the tongue coating. From this point of view, mechanical tools such as tongue brushes or scrapers have been developed. However, approaches by chemical tongue cleaning have not been reported. Thus we developed tablets containing protease from kiwifruits, which could resolve tongue coating, and assessed the effects of the protease tablet to control tongue coating.
Methods  Crossover studies and double blind experiments were designed using volunteers with informed consent. The trial was done twice per volunteer, that is, they had a tablet with or without the addition of protease from kiwifruits (test and placebo) with intervening washout periods of at least 2 weeks. The degree of change in tongue coating was evaluated visually using a tongue coating score which consisted of an area component (0–3) and a thickness component (0–3). An image analyzer was also used to measure the changing in actual area of coating.
Results  The average value of the tongue coating scores after taking a test tablet (11.4 ± 5.2) was significantly smaller ( P  < 0.01) than before taking the tablet (18.8 ± 7.0). Image analyzer measurements also showed significant reduction ( P  < 0.01) of tongue coating by taking test tablet. On the other hand, a placebo tablet showed no significant effects in both analyses.
Conclusions  This study indicated that taking protease tablets could reduce tongue coating. We are planning further clinical trials that can show reduced VSC concentrations in mouth air with decreasing tongue coating.