Peripheral blood stem cells used to augment autologous bone marrow transplantation

Peripheral blood stem cells (PBSC) were used to augment autologous bone marrow transplantation (ABMT), aiming to hasten engraftment after high dose treatment in a group of heavily pretreated patients. PBSC were obtained by leukapheresis during the rebound after standard chemotherapy. In 11 patients aged 7-17 years, high dose chemotherapy consisted of busulphan 16 mg/kg orally with melphalan 160 mg/m2 intravenously for seven patients, and melphalan 200 mg/m2 intravenously alone for four. The median number of granulocyte-macrophage colony forming units in the reinfused PBSC was 3.42 x 10(4)/kg (3.03-18.01) and bone marrow 12.4 x 10(4)/kg (4.16-28.6). Neutrophil recovery to > or = 0.5 x 10(9)/l and platelet transfusion independence occurred at a median of 14 days (11-18) and 22 days (9-84) respectively. In five patients the early engraftment was transient with neutrophils again dropping below 0.5 x 10(9)/l then slowly recovering. There was one toxic death due to sepsis. PBSC harvesting in these children was undertaken without interrupting routine chemotherapy and without the use of bone marrow growth factors. In some patients PBSC failed to influence engraftment and the use of combined chemotherapy and growth factor priming for PBSC collection may give improved results.     

Efficacy of Nebulised Epinephrine versus Salbutamol in Hospitalised Children with Bronchiolitis

Background

The use of bronchodilators in bronchiolitis lacks consensus. The efficacy of nebulised epinephrine versus salbutamol in bronchiolitis and the safety profile of the bronchodilators was studied.

Methods

Effects of nebulised epinephrine and salbutamol were compared in children with moderate to severe acute bronchiolitis. Thirty children between 2 to 24 months of age were recruited, 15 in each treatment group. Children received periodic (0,30,60 minutes followed by 4 hourly) doses of either 1:1000 laevo- epinephrine (0.5ml/kg subject to a maximum of 2.5ml with 3ml saline) or salbutamol (0.15mg/kg with 3ml saline) via nebuliser with oxygen. Changes in heart rate (HR), respiratory rate (RR), respiratory distress assessment instrument (RDAI), oxygen saturation (SpO2), oxygen requirement, duration of hospital stay and the side effects were studied.

Results

The respiratory status was better with significant improvement in RR, RDAI score and SpO2, decreased oxygen requirement and shorter hospital stay in the epinephrine group. There were no significant side effects in either group.

Conclusion

Nebulised epinephrine is a useful and safe drug for moderate/severe bronchiolitis and is superior to salbutamol.Key Words: Bronchiolitis, Nebulised bronchodilators, Epinephrine, Salbutamol     

Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology

Background  

There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT.     

中药对TGF β-Smad信号通路的干预作用

转化生长因子β1(transforming growth factor beta,TGFβ)是最重要的促肝纤维化因子之一,TGFβ-Smad信号转导通路是肝纤维化主要的信号转导通路.本文综述TGFβ-Smad信号通路与肝纤维化的关系,以及中药制剂对该信号通路的干预作用研究进展.     

Evaluation of CD44 variant 6 expression and clinicopathological factors in pulmonary metastases from colon carcinoma

Although relatively little is known about the molecular mechanisms underlying tumor progression, recently CD44 glycoproteins and the c-Met receptor tyrosine kinase have been identified as potentially important components of the metastatic cascade. CD44 is a family of transmembrane receptors generated from a single gene by alternative splicing and differential glycosylation. Important biological processes involving CD44 glycoproteins include cell adhesion, lymphocyte homing, hematopoiesis, tumor progression and metastasis. The precise mechanism via which CD44 promotes tumorigenesis have not yet been elucidated. We evaluated the expression of adhesion molecule CD44 variant 6 in pulmonary metastases from colorectal carcinomas and its correlation with clinicopathological parameters. Twenty patients were randomly selected from the patients who had undergone a resection of pulmonary metastasis from colorectal cancer. Formalin-fixed, paraffin-embedded archival specimens of tumor tissues and adjacent normal mucosa from these patients were the subjects of the present study. Immunoreactivity for CD44 was quantified. Specimens were considered positive if almost 25% of the neoplastic cells were stained. CD44 v6 expression was related to the interval between colon resection and metastases diagnosis, the number of pulmonary metastases, and the survival after lung resection. No statistical correlation was found between CD44 v6 positivity and disease-free interval after colon resection, number of metastases or 2-year survival after lung resection. Probably CD44 v6 is necessary and sufficient to confer metastatic potential to carcinoma cells increasing the migration capacity and participating in invasion via changes in adhesion to the extracellular ligands, but is not necessary to modify the clinical history of the metastases. Therefore the evaluation of CD44 v6 expression in lung metastases does not influence the therapeutic scheme.     

中药鳖甲品种鉴别的研究

目的：为了探索不同种源中药鳖甲的鉴别方法,方法;应用生药形态学和蛋白电泳实验方法对不同种源鳖甲进行鉴别。结果：５种不同种源的鳖甲在生药形态上有明显的区别。蛋白电泳实验表明不同种源的鳖甲具有不同的特征,其结果与形态学上区别相吻合。结论：生药形态学结合蛋白电泳实验可作为鉴别鳖甲品种的鉴定方法。     

Interindividual variation in the metabolic activation of heterocyclic amines and their N-hydroxy derivatives in primary cultures of human mammary epithelial cells

The heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP) are pyrolysis products formed when meat is cooked and are rodent mammary carcinogens. They are thought to be metabolically activated by N-hydroxylation, catalysed by cytochrome P450 (CYP), followed by O-acetylation catalysed by N- acetyltransferases. Primary cultures of human mammary epithelial cells (HMECs) prepared from up to 26 individuals for each compound, were treated with IQ, MeIQ, or PhIP (500 microM) or with N-hydroxy-2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) or N-hydroxy-2-amino- 3-methylimidazo[4,5-f]quinoline (N-OH-IQ) (20 microM) and the levels of adduct formation in their DNA analysed by 32P-post-labelling. In order to investigate whether pharmacogenetic polymorphisms influence DNA adduct formation, the NAT2 genotype of each individual was determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that distinguishes between the wild-type and four variant alleles. Presence of two variant alleles designates a slow NAT2 acetylator, whereas individuals with one or two wild-type alleles are designated fast NAT2 acetylators. Interindividual variations in total DNA adduct levels ranged for IQ from 0.64-63.1 DNA adducts per 10(8) nucleotides (mean 7.80), for MeIQ from 1.99-17.8 (mean 6.63), for PhIP from 0.13-4.0 (mean 0.96), for N-OH-PhIP from 6.32-497 (mean 176) and for N-OH-IQ from 0.92-30.6 (mean 9.24). The higher adduct levels observed in cells treated with the N-OH metabolites suggests that N- hydroxylation is the rate-limiting step in HMECs and this may be due to low CYP levels. In contrast, the Phase II reaction catalysed by N- acetyltransferases is probably the major step in the metabolic activation of heterocyclic amines that occurs in the breast. Higher mean levels of heterocyclic amine-DNA adduct formation were detected in the cells of NAT2 fast acetylators compared with slow acetylators, with mean adduct levels per 10(8) nucleotides following IQ treatment, of 12.74 and 3.57 respectively, following PhIP treatment, of 1.20 and 0.74, respectively, following MeIQ treatment, of 7.90 and 5.08, respectively and following N-OH-PhIP-treatment, of 243.1 and 130.0, respectively. However, due to the large variations in adduct levels, these differences in mean values were not statistically significant with the limited number of individuals studied. This appears to be the first pilot study to demonstrate interindividual variations in the metabolic activation of heterocyclic amines and their metabolic intermediates in primary cultures of HMECs in vitro.      

High prevalence of undiagnosed coeliae disease in 5280 Italian students screened by antigliadin antibodies

Many cases of coeliae disease are currently undiagnosed. We carried out a pilot study on screening for coeliae disease in a school population. The screening protocol consisted of three parts: (1) IgG and IgA antigliadin antibody (AGA) assay; (2) antiendomysium antibody and total serum IgA determinations; (3) jejunal biopsy. A total of 5280 students aged 11-15 years (71.7% of the eligible population) underwent the first evaluation; 113 subjects performed the second tests and 35 of these needed the third investigation. Coeliae disease was diagnosed in 23 cases, most of which were atypical or silent forms. The prevalence of undiagnosed coeliae disease was 4.36 per 1000 screened subjects (95% CI 2.58-6.14) and 5.03 per 1000 (95% CI 3.41-6.65) in the general population. The ratio of known to undiagnosed cases was 1 to 6.4. This high prevalence of undiagnosed coeliae disease raises a number of problems that require further evaluation.     

Technetium-99m sestamibi: an indicator of breast cancer invasiveness

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with ^99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revision showed a positive ^99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm² and one showed 99 microvessels/mm²; by contrast there were 71.6±12.1 microvessels/mm² in the nine N- and sestamibi-negative tumours. Our study suggests that ^99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour.