Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-I(Milano)-phospholipid complex

OBJECTIVES: In this study, we examined whether a reconstituted high-density lipoprotein (HDL) utilizing recombinant apolipoprotein A-I(Milano) (apo A-I(M))/phospholipid complex (PC) could restore normal endothelial function in hypercholesterolemic apolipoprotein (apo) E-null mice. BACKGROUND: We have previously shown antiatherosclerotic and vasculoprotective effects of recombinant apo A-I(M). METHODS: A perfused vessel preparation was used to examine vascular responses in control wild-type, untreated, and treated apo E-null mice. Aortic tissue cholesterol content and platelet aggregation were also measured. RESULTS: Endothelium-dependent vasodilator responses to acetycholine were significantly inhibited in untreated apo E-null mice compared with control wild-type mice (p < 0.001). Treatment of the mice for five weeks with once every-other-day intravenous bolus injections of apo A-I(M)/PC restored endothelium-dependent dilation in a dose-dependent manner (p < 0.01 at 80 mg/kg dose). The improvement in endothelial function was associated with a reduction in aortic cholesterol content and reduced platelet aggregability and occurred despite severe and persistent hypercholesterolemia. Neither treatment with free protein nor phospholipid carrier alone produced any significant effects. We performed additional experiments in vitro in isolated rabbit carotid arteries to compare the effects on lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Treatment with apo A-I(M)/PC prevented impairment of endothelium-dependent vasodilator responses to acetylcholine to a greater degree than either wild-type apo A-I or plasma-derived HDL. CONCLUSIONS: Our results indicate a rapid improvement in endothelial dysfunction with recombinant apo A-I(M)/PC that is associated with mobilization of tissue cholesterol. Taken together with previously established antiatherosclerotic and antithrombotic effects, these findings suggest significant vasculoprotective effects with apo A-I(M)/PC therapy.     

Angiotensin II AT1 receptor blockade improves renal perfusion in hypercholesterolemia

BACKGROUND: Hypercholesterolemia (HC) is a risk factor for renal disease that may activate the angiotensin II type 1 (AT1) receptor and accelerate renal damage. Early diet-induced HC impairs renal perfusion responses, but it is yet unknown whether the AT1 receptor is involved. This study tested the hypothesis that AT1 receptor blockade improved renal perfusion and functional responses in hypercholesterolemic pigs. METHODS: Regional renal hemodynamics and function in vivo were quantified bilaterally in pigs, at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside), using electron beam computed tomography after 12 weeks of normal (n = 6) or HC diet (n = 6), or HC diet supplemented (100 mg/d) with the AT1-receptor antagonist irbesartan (HC + AT1, n = 6). RESULTS: Basal cortical and medullary perfusion was similar among the groups. Basal tubular function was similar on normal and HC diets, whereas HC + AT1 showed decreased proximal and distal fluid reabsorption. Hypercholesterolemic pigs had blunted cortical perfusion (P = .22) and augmented tubular responses to acetylcholine, whereas on HC + AT1 diet, cortical perfusion (P = .002) and tubular function were similar to normal animals. This was associated with decreased systemic levels of the oxidative stress markers thiobarbituric acid reactive substances. CONCLUSIONS: The AT1 receptor blockade in HC improves renal perfusion and tubular functional responses to endothelium-dependent vasodilators, in association with a decrease in oxidative stress. These results imply involvement of the renin-angiotensin system in the blunted renal cortical perfusion responses observed in HC, and suggest a potential role for these agents in preservation of intrarenal hemodynamics and function in HC.     

Thoracic splenosis: A diagnosis by history and imaging

Abstract:   Thoracic splenosis (TS) is autoimplantation of ectopic splenic tissue in the thoracic cavity that occurs following splenic injury. The majority of cases of TS are asymptomatic and are diagnosed in the course of an evaluation of incidentally discovered pulmonary lesions. Some cases may be difficult to diagnose, especially if features suggesting TS are not recognized. This may lead to an extensive work-up and unnecessary invasive diagnostic procedures including thoracotomy. This case report describes a 40-year-old man, who was diagnosed incidentally with TS, several years after the initial injury. Multiple, asymptomatic, left-sided pleural based lesions associated with a history of thoracoabdominal injury and splenectomy are the key points that should alert suspicion of TS, which can then simply be confirmed by a Tc-99m sulphur colloid radionuclide scan. Most patients are treated conservatively unless they are symptomatic. Physicians must recognize the key features suggesting a diagnosis of TS, order appropriate imaging studies and avoid unnecessary invasive diagnostic procedures.     

Familial neonatal pneumothorax associated with transient tachypnea of the newborn

We describe neonatal spontaneous pneumothorax associated with transient tachypnea of the newborn in siblings of two families. Familial spontaneous pneumothorax is extremely rare in neonates. Was our observation just an incidental finding, or is there a familial predisposition to spontaneous pneumothorax? Pediatr Pulmonol. 2003; 36:69–72. © 2003 Wiley‐Liss, Inc.     

Interventricular mechanical dyssynchrony: a novel marker of cardiac events in Brugada syndrome.

BACKGROUND: Risk stratification in Brugada syndrome is controversial, especially in asymptomatic individuals. OBJECTIVE: The purpose of this study was to evaluate tissue Doppler echocardiography in risk stratification of Brugada syndrome. METHODS: Patients with Brugada ECG pattern were enrolled in the study. Left ventricular (LV) preejection period was defined as the time interval between onset of the QRS complex and onset of LV lateral wall systolic wave. Right ventricular (RV) preejection period was defined as the time interval between onset of the QRS complex and onset of RV lateral wall systolic wave. Delay in onset of contraction between RV and LV was defined as RV preejection time - LV preejection time [PET((RV-LV))]. RESULTS: Type 1, 2, and 3 Brugada ECG pattern was found in 30, 56, and 31 patients, respectively. PET((RV-LV)) was significantly greater in type 1 Brugada patients (39.2 +/- 3.2 ms) compared with type 2 (5 +/- 0.3 ms) and 3 (5 +/- 0.4 ms) Brugada patients as well as controls (4.6 +/- 0.3 ms, P <.01 for all comparisons). Among type 1 Brugada patients, PET((RV-LV)) was significantly greater in patients who had previous cardiac events compared with asymptomatic subjects (48.2 +/- 4.3 ms vs 29.5 +/- 3.6 ms, P <.05). In the presence of type 1 Brugada ECG pattern, PET((RV-LV)) > or =40 ms identifies patients likely to have cardiac events, with 85.7% sensitivity and 93.7% specificity. CONCLUSION: PET((RV-LV)) is an important risk indicator for Brugada syndrome.     

Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia

Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the purine analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/c x C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabine-treated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals (P=0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versus-leukemia appeared to be augmented in the same animals.     

How safe is primary knee replacement surgery? Perioperative complication rates in Northern Illinois, 1993–1999

Objective

To describe inpatient complications for primary total knee replacement (TKR) in a period of rapidly growing orthopedic surgery capacity, declining length of stay, and more frequent discharge to rehabilitation facilities.

Methods

Complication incidence according to published coding algorithms was estimated for 35,531 primary TKR admissions of northern Illinois residents to 65 Illinois hospitals. Complication odds were estimated as a function of patients' clinical and sociodemographic status, hospital volume, residency training, TKR length of stay, International Classification of Diseases, Ninth Revision (ICD‐9) coding intensity, and discharges to skilled nursing or rehabilitation facilities.

Results

Primary TKR admissions increased 36% between 1993 and 1999, length of stay declined 43%, average ICD‐9 code use increased 31%, and rehabilitation discharges increased 68%. Major complication rates declined 44% (12.4% to 6.9%; P < 0.0001) over this period, reflecting a 50% reduction in the adjusted odds of complication between 1993 and 1999. There was no association of procedure volume and outcome.

Conclusion

It is likely that the reduction in complications reflects true safety improvements as well as reduced length of stay.

     

Comparative analysis of Bayer wide-range C-reactive protein (wr-CRP) and the Dade-Behring high sensitivity C-reactive protein (hs-CRP) in patients with inflammatory bowel disease

OBJECTIVE: The recently introduced Bayer wide‐range C‐reactive protein (wr‐CRP) assay might be relevant for the real‐time low‐cost and online determination of inflammatory bowel disease (IBD) activity. Our aim was to examine whether wr‐CRP can substitute for the Dade Behring high sensitivity C‐reactive protein (hs‐CRP) assay in IBD patients. METHODS: A total of 71 patients with IBD, of whom 48 had Crohn's disease CD and 23 had ulcerative colitis (UC) with various intensities of disease activity participated in the study. The CRP of patients who were under treatment at the Department of Gastroenterology and Liver Diseases were measured using both wr‐CRP and the hs‐CRP. RESULTS: A significant (r = 0.995; P < 0.001) correlation was noted between the hs‐CRP and wr‐CRP measurements for the whole sample as well as for the two diseases, CD (r = 0.994; P < 0.001) and UC (r = 0.997; P < 0.001), which were analyzed separately. CONCLUSION: The Bayer wr‐CRP assay might be a useful low‐cost and real‐time inflammation‐sensitive biomarker in patients with IBD.     

18F‐Fluorodeoxyglucose (FDG)‐PET features of focal nodular hyperplasia (FNH) of the liver

Abstract: Aim: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by ¹⁸F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET). Methods: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F‐FDG PET imaging. The lesions were found incidentally. The 18F‐FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300–370 MBq 18F‐FDG. The 18F‐FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm±2.37) and from 1.5 to 6 cm (mean 3.28±1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F‐FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F‐FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12±0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07±3.79). The SUV corrected for LMB (SUV_LBM) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81±0.41) for FNH and between 5.9 and 16.3 (mean 9.15±4.03), respectively. Conclusion: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F‐FDG‐PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.