No effect of stem cell mobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction

Abstract. Objectives: To evaluate the effect of bone marrowpluripotent stem cell mobilization with granulocyte-monocyte colony stimulating factor (GMCSF) on infarct size and left ventricular function, in the setting of acute myocardial infarction, with a protocol easily applicable in clinical practice. Methods: Ten pigs underwent left thoracotomy and left anterior descending coronary artery occlusion for 1 h, followed by reperfusion. After 50 min of arterial occlusion, the animals were randomly divided between treatment with placebo (Group 1) and subcutaneous GM-CSF (Group 2). The thoracotomy was closed and the animals recovered. In Group 2, GM-CSF, 20 µg/kg, was administered daily, 5 days/week, for 3 weeks. Echocardiograms were obtained at 5 and 28 days after acute myocardial infarction. At 30 days, infarct size, expressed as a percentage of the whole left ventricular mass, was measured. Results: The white blood cell count increased from 13000 ± 3338/µl to 28700 ± 4916/µl (p = 0.001) in the GM-CSF-treated group. Infarct size was 7.8 ± 6.1% in Group 1 vs 7.5 ± 7.7% in Group 2 (ns). Similarly, no significant difference was observed between the 2 study groups in any of the echocardiographic measurements made at 28 days. Conclusions: Subcutaneous GMCSF administered during the early post acute myocardial infarction period neither decreased infarct size nor improved left ventricular function. Other protocols for mobilization of stem cells and their concentration in the injured area should be developed to combine efficacy and clinical applicability.     

16例脑结核瘤抗结核治疗系列观察

目的:报告16例颅内结核瘤患者的临床、影像学表现及抗结核治疗的结果.设计:本文共纳入苏丹Khartoun市全国神经系统疾病中心连续观察的16例脑结核瘤患者.诊断则依据其临床、头颅影像学特征及对抗结核治疗有效等方面.本组中共有7例具有脑组织或脑外组织的病理组织学资料.结果与结论:本组病例最常见的临床表现是头痛(100%)、全身性抽搐(68.7%)及偏瘫(56.2%).头颅横断面电子计算机体层摄影(CT)/核磁共振成像(MRI)显示单个或多个明显增强的病变及病灶周围水肿.经抗结核治疗后,多数存活患者(13/15)病变完全吸收.病变部分吸收与就诊延迟、颅内多个大病灶及晚期粟粒性结核病有关.我们主张对颅内结核瘤,即使是拟诊病例,应早期经验性试用抗结核治疗,尤其在结核病高发地区.     

Decreased accessibility of platelet-bound fibrinogen to antibody and enzyme probes

The binding of fibrinogen to platelets is a multiphasic process leading to apparently nonreversible associations between fibrinogen and stimulated platelets. To further investigate changes in platelet- fibrinogen interactions, the present study examined the accessibility of platelet-bound fibrinogen and its GPIIb-IIIa receptor to antibody and enzyme probes as a function of time after platelet stimulation with adenosine diphosphate (ADP). Whereas only minimal changes in fibrinogen and 10E5 binding were observed within 60 minutes after platelet stimulation and equilibrium fibrinogen binding, the binding of polyclonal antifibrinogen antibodies decreased significantly (75% +/- 13%, mean +/- SD, n = 9). Similar decreases were noted with rabbit antifibrinogen Fab and F(ab')2 fragments. In addition, plasmin (32 mU/mL) added to platelets five minutes compared with 60 minutes after equilibrium fibrinogen binding dissociated 52% +/- 12% compared with 33% +/- 7% of platelet-bound fibrinogen in five minutes, and 83% +/- 15% compared with 66% +/- 14% of bound fibrinogen in 15 minutes. No difference in plasmin cleavage products was observed, however, by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE). Complete fibrinogen dissociation occurred 30 minutes after plasmin addition, confirming that fibrinogen was not internalized. In contrast, dissociation of platelet-bound fibrinogen by chymotrypsin was less affected by time after equilibrium fibrinogen binding, and minimal changes in antifibrinogen antibody recognition and plasmin-induced dissociation of fibrinogen bound to stimulated but glutaraldehyde-fixed platelets were observed. The data suggest that ADP-induced fibrinogen binding to fresh platelets is accompanied by progressive rearrangements of fibrinogen on the platelet surface.     

Histomorphometric analysis of aplastic bone disease in chronic renal failure at initiation of haemodialysis: Relation to aluminum and parathormone

SUMMARY: We studied bone histology of 134 uraemic patients without a history of vitamin D administration at the start of haemodialysis. Patients were categorized according to bone histology as follows: aplastic bone disease (ABD), ostitis fibrosa, mixed type, mild hyperparathyroidism and osteomalacia. On initiation of haemodialysis, ABD was observed in 48.5% of patients. the average age of the ABD group (50.8 ± 12.5 years) was significantly higher than that of patients with other histologies ( P <0.01). Serum parathyroid hormone (PTH) and alkaline phosphatase (ALP) concentrations were lower ( P <0.01) in the ABD group, especially in patients with diabetes mellitus. Patients with diabetes mellitus and ABD had lower serum concentrations of PTH and ALP than non-diabetic patients, suggesting that depressed PTH may be related to ABD. Eleven (55%) of the 20 patients who were receiving A1(OH)₃ also had ABD. A direct relationship was observed between serum aluminum concentration and aluminum-positive bone surface ( r =0.60; P <0.01). Aluminum staining was more frequently observed in the ABD group than in the non-ABD group ( P <0.01). Because serum intact-PTH concentrations correlate with osteoid surface area, fibrosis volume and bone formation rate, it may be a useful marker of bone histology in renal osteodystrophy. These results suggest that, in addition to conservative treatment with A1(OH)₃, other factors may be involved in the formation of ABD which is often present at the start of haemodialysis.     

The Kallmann syndrome gene product expressed in COS cells is cleaved on the cell surface to yield a diffusible component

Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia and caused by a defect of migration and targeting of gonadotropin-releasing hormone-secreting neurons and olfactory axons during embryonic development. We previously cloned the gene responsible for the X-linked form of the disease encoding a 680 amino acid protein, KAL, which displays the unusual combination of a protease inhibitor domain with fibronectin type III repeats. Previous expression studies by northern blot and RNA in situ hybridization in human and chick indicated that the gene is expressed at very low levels in the olfactory bulb during development. Therefore, low abundance of the protein has hampered a detailed biochemical characterization. By overexpressing both the human and chick KAL cDNAs in eukaryotic cells, we now provide evidence that KAL is a glycosylated peripheral membrane protein with an apparent molecular weight of approximately 100 kDa. We show that this 100 kDa protein is proteolytically processed on the cell membrane to yield a 45 kDa diffusible component, which is detectable with an antisera against the C-terminal part of the protein and binds tightly to cell surfaces. These data provide a first step toward understanding KAL function in neuronal interactions and neurite extension in the olfactory bulb and suggest that KAL might be a diffusible chemoattractant molecule for olfactory axons.      

Ventilatory response to exercise and kinetics of oxygen recovery are similar in cardiac transplant recipients and patients with mild chronic heart failure.

BACKGROUND: Exercise capacity, assessed by cardiopulmonary exercise treadmill testing (CPET), does not return to normal following heart transplantation. This study evaluated the ventilatory response to exercise and the kinetics of oxygen (O(2)) recovery in heart transplant recipients (HTR) compared to healthy volunteers (HV) and heart failure patients. METHODS: Eighteen patients with end-stage heart failure (ESHF), 12 with mild heart failure (MHF) matched for peak oxygen consumption (Vo(2)) with the HTR, 12 HTR and 12 HV underwent CPET for measurements of peak Vo(2), Vo(2) at anaerobic threshold (AT), first-degree slope of Vo(2) decline during early recovery (Vo(2)/t-slope), time required for a 50% fall from peak Vo(2) (T(1/2) of Vo(2)) and the slopes of VE/Vco(2) and VE/Vo(2). RESULTS: The MHF and HTR groups had similar ventilatory responses to exercise and O(2) recovery kinetics. Peak Vo(2) (18.5 +/- 5.7 vs 9.4 +/- 0.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 6.7 +/- 1.8 ml/kg/min, p < 0.001) and Vo(2)/t-slope (0.6 +/- 0.2 vs 0.3 +/- 0.2 liter/min/min, p = 0.055) were higher in the HTR than in the ESHF group. In contrast, HTR had lower VE/Vco(2)-slope (31.4 +/- 3.8 vs 39.2 +/- 9.9, p = 0.015) and T(1/2) Vo(2) (1.5 +/- 0.3 vs 2.4 +/- 1.1 minute, p = 0.014) than the ESHF group. Compared to HV, HTR had lower Vo(2) peak (18.5 +/- 5.7 vs 28.4 +/- 6.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 19.8 +/- 4.5 ml/kg/min, p = 0.04), Vo(2)/t-slope (0.6 +/- 0.2 vs 1.0 +/- 0.4 liter/min/min, p = 0.005) and steeper VE/Vco(2) slope (31.4 +/- 3.8 vs 23.6 +/- 2.7, p = 0.062). Heart rate deceleration during recovery was significantly slower in HTR than in all other groups. CONCLUSIONS: Exercise intolerance and delayed O(2) recovery kinetics were only partially reversed after heart transplantation. This finding suggests that some of the pathophysiologic mechanisms of heart failure persist after heart transplantation.     

Assesment of polyunsaturated fatty acids in cord blood of infants of diabetic mothers

Objective：To assess whether infants of diabetic mothers [ pre pregnancy diabetics （PPD） and gestational diabetics mellitus （GDM） ] have compromised arachidonic and docosahexaenoic acids in their plasma and the relationship with deficiency of the same compounds in their mothers. Methods： This study was conducted on 30 diabetic mothers （ both PPD and GDM） and their infants. Twenty healthy infants and their mothers with age and sex matched were included as controls. All infant （ of diabetic and non diabetic mothers） were subjected to assessment of APGAR Scoring, thorough history taking and anthropometric measures. Lipid profile components as well as polyunsaturated fatty acids（PUFA） were assessed in diabetic GDM and PPD and non diabetic mothers as well as in their babies. Results ： High-density lipoproteir（HDL） level was found to be significantly lower in diabetic mothers （specially those with PPD） compared to non diabetic ones, whereas no significant difference was found between babies of the two groups. Also, the current study revealed that diabetic mothers （ GDM and PPD） and their babies had significantly higher levels of PUFA precursors linoleic acids （LA） and alpha linoleic acids（ALA）. PUFA arachidonic acid（AA） and docosahexaenoic acids（DHA） were found to be significantly lower in diabetic mothers （GDM and PPD） compared to non diabetic mothers, and same results were found in the babies of the two groups. Conclusion： Neonates with diabetic mothers （both GDM and PPD） have highly compromised plasma levels of AA and DHA PUFA, which affects the child well being by far, and produces hazardous muhi-system complications on the long run.     

Unilateral pulmonary edema due to pulmonary venous obstruction from fibrosing mediastinitis

An unusual case of fibrosing mediastinitis with obstruction of the inferior and superior left pulmonary veins and severe narrowing of the right pulmonary artery, disclosed after unilateral pulmonary edema, is described. The 18-year-old male patient had a long history of cough, progressive dyspnea and recurrent hemoptysis and the possible diagnosis of "interstitial fibrosis" from a previous lung biopsy. The diagnosis and the pulmonary vessels involvement were suspected after right heart catheterization combined with transesophageal echocardiography and confirmed during urgent thoracotomy and at postmortem examination.