"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

From recipe to research: introducing undergraduate students to the nature of science using a hybrid practical course centred on drug discovery for neglected diseases

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Mucosal protection by sucralfate and its components in acid-exposed rabbit esophagus

Sucralfate has been reported to protect the esophageal epithelium of the rabbit and cat against acid injury. To determine the contribution of its components, aluminum hydroxide and sucrose octasulfate (SOS), rabbit esophageal epithelia were mounted in Ussing chambers to monitor changes in electrical resistance (R) upon exposure to HCl (pH 1.4-1.6). In untreated tissues, acidification of the luminal bath produced a progressive decline in R, indicating increased epithelial permeability. Sucralfate added to the luminal bath 45 min after acidification increased R to preexposure levels--an effect accompanied by increased luminal pH. Similar to sucralfate, aluminum hydroxide added to the acidified bath increased R and luminal pH. However, the effect of aluminum hydroxide could be abolished by titration with HCl to maintain pH similar to acid-treated control tissues. Tissues treated with sucralfate and whose luminal solutions were titrated with HCl to maintain pH similar to controls no longer exhibited an increase in R but, in contrast to aluminum hydroxide treatment, the acid-induced decline in R was prevented. This action of sucralfate was shown to be a property of its other component, SOS. Sucrose octasulfate, like acid-titrated sucralfate solutions, did not increase luminal bath pH, yet prevented the acid-induced decline in R. Confirmation of protection by SOS was shown by additional morphologic and flux studies. Thus 1 h after luminal bath acidification in the Ussing chamber, SOS-treated tissues demonstrated less damage (injury score 0.6 +/- 0.4 vs. 1.6 +/- 0.3, p less than 0.05) and lower permeability to mannitol (0.003 +/- 0.001 vs. 0.013 +/- 0.005 mumol/h X cm2, p less than 0.05) than untreated tissues. Similarly, 1 h of luminal perfusion with HCl in vivo produced less damage (injury score 1.3 +/- 0.5 vs. 3.5 +/- 0.4, p less than 0.05) and less H+ efflux from the lumen in SOS-treated than untreated tissues. These results indicate that sucralfate can protect against acid injury in esophagus and that this protection is mediated by (a) intraluminal pH buffering through its content of aluminum hydroxide and (b) enhancing mucosal defense against H+ entry and injury through its content of SOS.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

A statistical analysis of murine stem cell suicide techniques

The clinical application of soft agar cloning techniques for granulocyte-macrophage stem cells (CFU-C) has resulted in a number of contradictory reports that may in part be due to an inadequate data base. Growth of murine CFU-C is more reproducible and less variable than that of human CFU-C. We utilized in vivo hydroxyurea suicide of murine marrow CFU-C to address the question of how many experiments are needed to detect a specific difference with a p of less than 0.05. In 66 experiments the mean marrow CFU-C hydroxyurea kill was 23.3%; 6-9 separate experiments were necessary to detaect differences of 25%-30%. In order to be sure that a 25%-30% difference is not present, 15-21 experiments were required. Using a Dec-20 computer, 1000 samples of sample size 3, 4, or 10 were drawn from the 66 experiments; it was found that with 3 experiments and a true value of 23%, the actually observed value was below 10%, 17% of the time, and was over 40% in 10% of the samplings. In a smaller number of experiments similar results were obtained analyzing 3HTdR suicide of pluripotent stem cells and CFU- C. These data could provide a base from which to judge the validity of studies utilizing the CFU-C technique.     

小唾液腺癌治疗新进展

该文旨在对小唾液腺癌的治疗进行回顾。小唾液腺癌可发生在头颈部很多位置,通常表现为黏膜下肿块。影像学检查是对肿瘤发病部位及病变范围内解剖结构的关系进行评估的基础。切取活检或穿吸活检可以决定肿瘤的病理类型和分级。随着分子生物学技术的不断进步,小唾液腺癌的诊断     

Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study

Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1?year followed by 2?years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1?year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P?相似文献