Chest physiotherapy in infants with cystic fibrosis: To tip or not? A five‐year study

There is controversy about the need for postural drainage physiotherapy in asymptomatic infants with cystic fibrosis (CF). We aimed to compare the effectiveness of standard postural drainage chest physiotherapy (SPT) with a modified physiotherapy regimen without head-down tilt (MPT) in young infants with CF. Twenty newly diagnosed infants with CF (mean age, 2.1 months; range, 1-4) were randomized to SPT or MPT. Parents kept a detailed symptom and treatment diary for the following 12 months. Serial chest radiographs, taken at diagnosis, 12 months, 2(1/2) years, and 5 years after diagnosis, were assessed using the Brasfield score. Pulmonary function tests were compared between groups after 5 years. Of the 20 infants, 16 (80%) completed the review at 12 months, and 14 (70%) at 2(1/2) and 5 years. Patients receiving SPT had more days with upper respiratory tract symptoms than those on MPT (70 +/- 32.8 vs. 37 +/- 24.9 days; P = 0.04) and required longer courses of antibiotics (23 +/- 28.5 vs. 14 +/- 11.2 days; P = 0.05). Chest x-ray scores were similar at diagnosis but were worse at 2(1/2) years for those receiving SPT (P = 0.03). Forced vital capacity and forced expired volume in 1 sec (FEV(1)) at 5-6 years was lower for SPT than for MPT (P < 0.05). In conclusion, MPT was associated with fewer respiratory complications than SPT in infants with CF.     

Trophoblasts reduce the vascular smooth muscle cell proatherogenic response

Maternal spiral artery remodeling is the consequence of controlled trophoblast invasive interaction with the maternal cellular environment and is fundamentally important for successful placentation. In preeclampsia, trophoblast invasion is shallow, remodeling is incomplete, and vessels develop an inflammatory appearance, termed "acute atherosis." We noted that, in our preeclampsia, human renin-human angiotensinogen transgenic rat model, complement component 3 (C3), and tumor necrosis factor-alpha were upregulated and heavily expressed in atherotic uteroplacental vessels. We next used coculture involving human trophoblasts, rat vascular smooth muscle cells (VSMCs), and human VSMCs to observe VSMC-trophoblast regulatory interactions. Tumor necrosis factor-alpha induced complement C3 and interleukin-6 expression in VSMCs. We found that trophoblasts were able to reduce VSMC C3 and interleukin-6 expression after the VSMCs were stimulated with tumor necrosis factor-alpha. However, a direct VSMC-trophoblast cell-cell contact was necessary for this anti-inflammatory response. We also studied double-transgenic VSMCs that express inflammatory components and exhibit accelerated proliferation ("synthetic" phenotype). Trophoblasts could not downregulate C3 in these cells. We then examined uteroplacental tissues from preeclamptic and control patients. In control deciduas, only traces of C3 staining were observed, and vessels were thin walled without thrombus formation. In preeclampsia, the decidual vessels showed atherosis, thrombus formation, and C3 expression. Our data suggest that fetally derived trophoblasts require direct cell-cell contact with maternally derived VSMCs to downregulate VSMC C3 and interleukin-6 expression and to avoid atherosis. The findings also implicate C3 in the placental vasculopathy observed in preeclampsia.     

Randomized, double-blind, multicenter study of the polymer-based 17-beta estradiol-eluting stent for treatment of native coronary artery lesions: six-month results of the ETHOS I trial.

OBJECTIVES: The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-beta estradiol-eluting R-Stent versus uncoated control stents for the treatment of patients with single de novo native coronary lesions. BACKGROUND: Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis. METHODS: Ninety-five patients were randomized to receive a slow-release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS). RESULTS: Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% +/- 14%, 33% +/- 11%, and 31% +/- 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 +/- 0.49 mm, 0.86 +/- 0.53 mm, and 0.84 +/- 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31). CONCLUSIONS: In this first-in-man randomized trial, the 17-beta estradiol-eluting R-Stent, in either slow- or moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.     

Novel insights into uremic vascular calcification: role of matrix Gla protein and alpha-2-Heremans Schmid glycoprotein/fetuin

Cardiovascular mortality is markedly increased in the dialysis population when compared to non-uremic subjects. Vascular and valvular calcifications are most frequently found in dialysis patients at risk and are independent predictors of cardiovascular death in this population. Traditionally, the presence of hyperphosphatemia and an increased calcium x phosphate product was considered a major pathomechanistic condition leading to excessive vascular and soft-tissue calcifications in uremic subjects. Recent studies in knockout mice, however, revealed that deficiencies in calcium-regulatory proteins may also directly contribute to the development of extraosseus calcifications. alpha(2)-Heremans Schmid glycoprotein and matrix Gla protein are important inhibitors of calcification in vivo and there is novel evidence available that a deficiency in such proteins is involved in the pathogenesis of cardiovascular calcifications in dialysis patients.     

Monitoring acetylsalicylic acid effects with the platelet function analyzer PFA-100

The efficacy of acetylsalicylic acid (ASA) to prevent thrombotic or embolic events in patients with atherosclerosis was demonstrated in many large trials. Despite this fact, a subpopulation of patients experiences acute myocardial infarction or cerebrovascular ischemia indicating a nonresponsiveness to ASA. These patients would be candidates for an alternative or additional antiplatelet therapy, if they could be reliably identified. The aim of the monitoring of ASA therapy should be the identification of nonresponders to prevent a long-term intake of the drug without adequate benefit, to justify a dose escalation, or to initiate an alternative antiplatelet drug therapy. Considerable progress has been made in the measurement of platelet function. One of the novel devices employed is the platelet function analyzer PFA-100, which was already tested in several studies involving patients with atherothrombosis to detect nonresponsiveness to ASA. Many of these investigations indicate that the PFA-100 could be used for routine identification of nonresponders to ASA and--probably also--for tailoring antiplatelet therapy. The aim of this article is to summarize the data obtained from the studies focusing on the monitoring of ASA therapy by the PFA-100.     

Autologous human keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid for grafting in nonhealing diabetic foot lesions: a pilot study

Diabetic foot complications are the most common cause of nontraumatic lower extremity amputations in the industrialised world. Unsatisfactory healing requires advanced therapeutic strategies, such as the use of skin grafts, which may represent a helpful option for wound coverage. Alternatively, a method using autologous keratinocytes grown to thin sheet grafts is available. The purpose of this pilot study was to investigate the application of autologous human keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid (Laserskin autograft) to diabetic foot ulcers. We studied 14 patients with type 2 diabetes mellitus and a nonhealing diabetic foot lesion, defined as existing longer than 6 months or with no wound healing apparent for 12 weeks. Between 7 and 64 days after the transplantation (depending on the size of the ulceration), 11/14 of the lesions were completely healed. The transplantation of autologous keratinocytes may allow faster closure of diabetic foot lesions and subsequently reduce length of hospitalization. This method can easily be planned with regard to logistics and time, and furthermore, this therapy option can be carried out by the diabetologist.     

High-dose chemotherapy with peripheral blood stem cell transplantation for patients with advanced ovarian cancer

Purpose: We report the results of high-dose chemotherapy (HDC) with peripheral blood stem cell transplantation in twenty-one patients with primarily advanced or relapsed ovarian cancer. Methods: Twenty-five women underwent stem cell collection, and 21 were finally treated with different regimens of HDC containing cyclophosphamide, etoposide, carboplatin, and treosulfan. The patients received cyclophosphamide ± cisplatin and cisplatin + paclitaxel, respectively, followed by G-CSF (n=24) or GM-CSF (n=1) for stem cell mobilization. Results: A mean of 7.2 ± 6.1 × 10⁶ CD34+ cells per kg bw were collected. Thirteen patients received double transplants and one patient received a triple transplant. The median age was 47 years (range 24–61 years) and the mean number of prior regimens was three (range 1–8). Engraftment occurred on time in all patients and there was one treatment-related death resulting in an overall mortality rate of 4.8% among the 21 patients treated with HDC. The response rate was 72% (48% CR, 24% PR) and the mean time to progression and overall survival after HDC were 7 and 32 months, respectively. Conclusion: HDC could be performed safely in patients with advanced ovarian cancer. However, even with a high response rate, the duration of response is short, warranting new treatment approaches to further improve the outcome of this population of patients with unfavorable prognosis. Received: 19 July 2000 / Accepted: 25 August 2000     

Endoscopic Doppler ultrasound after injection therapy for peptic ulcer hemorrhage

BACKGROUND/AIMS: A positive Doppler signal in endoscopic Doppler ultrasound at index endoscopy predicts a high risk for rebleeding from peptic ulcer. The aim of this study was to evaluate if a negative Doppler status immediately after injection therapy may exclude a rebleeding from peptic ulcer in a high-risk cohort. METHODOLOGY: Twenty consecutive patients (pts) (age: 68 (33-91) yrs; 11 female) with peptic ulcer bleeding were enrolled. All patients with an actively bleeding ulcer and those with a non-actively bleeding, but Doppler-positive ulcer were treated by injection of adrenaline (1:10,000 dilution). Treatment was performed during index endoscopy until the Doppler status was negative. Patients were followed-up clinically and endoscopically (including Doppler ultrasound) for bleeding recurrence. RESULTS: Patients were treated by injection of 12 (6 to 20) mL of adrenaline solution until Doppler scan was negative. During follow-up four pts (20%) had a clinically overt rebleeding episode. At control endoscopy three ulcers were actively bleeding and another two were Doppler positive without rebleeding (total: five of eighteen (27.7%) Doppler-positive ulcers). Two of the twenty pts required surgical therapy due to rebleeding (10%). CONCLUSIONS: A negative endoscopic Doppler status immediately after injection therapy is not helpful to identify patients with no risk for rebleeding from peptic ulcer.