A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient

By comparison of mass spectra from a small cohort of nipple aspiration fluids (NAF), we previously discovered a panel of five candidate breast cancer biomarkers among them an unidentified 4.7 kD peptide BF5. The purposes of the present study were to verify the presence of BF5 in an independent cohort; to determine the protein identity of BF5; and to provide insight into the biology of BF5 production and elevation in tumor-associated NAF. We prospectively collected bilaterally matched NAF from patients with unilateral Stage I/II breast cancer (IBC-31), ductal carcinoma in situ (DCIS-6), atypical ductal hyperplasia (ADH-5), and presumed healthy women who came to routine mammography and had a normal exam (31). Following the consolidation of its cancer-associated expression on SELDI-mass spectrometry, BF5 was isolated by gel electrophoresis and sequenced by tandem mass spectrometry. BF5 was elevated in 15–25% of women with IBC, DCIS, or ADH vs. 0% of controls. This elevation was restricted to the affected breasts. BF5 was identified as 41/42-aa C-terminal peptide of alpha1-antitrypsin (AAT), the principle inhibitor of serine protease neutrophile elastase. The full length AAT showed a consistent expression pattern as C-41/42, and C-41/42 can be generated in vitro by MMP-7 cleavage. In conclusion, elevated C-41/42 is likely the result of elevated AAT synthesis, and the activity of specific MMPs present within the tumor. As other C-terminal fragments of AAT are reported to function as tumor-derived suppressors to the host immune-system, elevated C-41/42 may also be predictive of a poor outcome.     

Severe accidents due to windsurfing in the Aegean Sea.

Windsurfing is a popular sport and has recently become an Olympic event. As an open-air water activity that requires the participant to be in perfect physical condition, windsurfers may be prone to accidents when certain basic rules or procedures are violated. The current study monitored severe injuries due to windsurfing over a period of 12 months in the Aegean Sea in Greece. Our study revealed 22 cases of severe accidents due to windsurfing, with a wide range of injuries including head injuries, spinal cord injuries, and severe fractures of the extremities. Prolonged hospitalization, severe disability and two deaths occurred as consequences of these accidents. The study examined the characteristics of these patients and the possible risk factors and conditions associated with the accidents. We also focused on the most common types of injuries and reviewed the mechanisms that may provoke them. Water sports and particularly windsurfing represent a major challenge for the emergency medical system, especially in the Aegean Sea. Hundreds of islands, kilometres of isolated coasts, millions of tourists, an extended summer period and rapidly changing weather create conditions that constantly test the efficacy of the emergency services. The development of an appropriate infrastructure and maximum control of the risk factors causing these accidents could reduce the morbidity and mortality that, unfortunately but rather predictably, accompany this popular summer activity.     

Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS

Objective: To determine the concentration of proteins and phospholipids, markers of inflammatory reaction such as platelet-activating factor (PAF), and cell alterations in bronchoalveolar lavage (BAL) fluid during the evolution of the acute respiratory distress syndrome (ARDS). Design: Prospective controlled study. Setting: 14-bed medical-surgical intensive care unit in a 750-bed university teaching hospital. Patients: 19 mechanically ventilated patients, 9 patients with ARDS and 10 patients without cardiopulmonary disease (controls), were eligible for this study. Interventions: BAL was performed during the early, intermediate, and late phases of ARDS. Measurements and results: Total phospholipids and individual phospholipid classes of the surfactant, proteins, PAF, and cells were measured. High levels of PAF, an increase in neutrophils and proteins, and quantitative as well as qualitative alterations in phospholipids in BAL fluid were observed in ARDS patients compared to the control group. PAF, proteins, and neutrophils were higher in early ARDS than in intermediate or late ARDS. The surfactant pool increased in the early phase and decreased in the intermediate or late phase of the syndrome. The qualitative alterations of surfactant consist of reduced phospholipid content in the surfactant structures with good surface properties; moreover, there was a considerable decrease in the percentage of phosphatidylcholine and phosphatidylglycerol, followed by an increase in phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in all three phases of ARDS compared to the control group. Lyso-phosphatidylcholine was detectable only in late ARDS. Conclusion: Total surfactant phospholipids, surfactant components, and inflammatory markers such as PAF, cells, and proteins were affected in patients with ARDS. These factors, undergoing quantitative alterations during the course of ARDS, could have a significant role in the pathogenesis and evolution of ARDS. Received: 8 July 1997 Accepted: 17 December 1997     

Mycotic aneurysm of the inferior pancreaticoduodenal artery: successful nonoperative management

Although mycotic aneurysms of small visceral arteries are rare, they have a high morbidity and mortality due to rupture and sepsis. Any patient with abdominal pain and bacterial endocarditis should be suspected of having a mycotic aneurysm. Selective arteriography confirms the diagnosis. In the case we have reported, diagnosis of a mycotic aneurysm of the inferior pancreaticoduodenal artery was established by angiography, and the patient was treated by percutaneous transcatheter embolization. This case demonstrates that mycotic aneurysms of small visceral arteries may be managed nonoperatively with antibiotics and percutaneous transcatheter embolization therapy.     

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

Scanning Electron Microscopy Observations of Failures of Implant Overdenture Bars: A Case Series Report

Background: Soldered or cast bars are used as a standard of care in attachment systems supporting maxillary and mandibular implant overdentures. When failures of these bars occur, currently there is a lack of evidence in relation to their specific etiology, location, or nature. Purpose: To investigate the failure process of a case series of six failed soldered bars, four intact soldered bars, and one intact cast milled bar, which had been supporting implant overdentures. Materials and Methods: A total of 11 different overdenture bars were removed from patients with different configuration of opposing arches. A failed bar (FB) group (n = 6) had failed soldered overdenture bars, which were recovered from patients following up to 2 years of wear before requiring prosthodontic maintenance and repair. An intact bar (IB) group (n = 5) had both soldered bars and a single cast milled bar, which had been worn by patients for 2 to 5 years prior to receiving other aspects of prosthodontic maintenance. All bars were examined using scanning electron microscopy to establish the possible mode of failure (FB) or to identify evidence of potential failure in the future (IB). Results: Evidence of a progressive failure mode of corrosion fatigue and creep were observed on all the FB and IB usually around the solder areas and nonoxidizing gold cylinder. Fatigue and creep were also observed in all the IB. Where the level of corrosion was substantial, there was no evidence of wear from the matrices of the attachment system. Evidence of an instantaneous failure mode, ductile and brittle overload, was observed on the fracture surfaces of all the FB, within the solder and the nonoxidizing gold cylinders, at the solder/cylinder interface. Conclusion: Corrosion, followed by corrosion fatigue, appears to be a key factor in the onset of the failure process for overdenture bars in this case series of both maxillary and mandibular overdentures. Limited sample size and lack of standardization identify trends only but prevent broad interpretation of the findings.     

Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for reexcisions

In breast conservation therapy, the margin status of the specimen predicts local recurrence and determines the need for reexcision. Many surgeons now take, at the time of lumpectomy, multiple separate "cavity margins" (CM) (the entire wall of the residual cavity) as final margins that supersede the oriented lumpectomy margins (LMs). We studied the efficacy of this method in 126 patients (23 with ductal carcinoma in situ [DCIS] only and 103 with invasive carcinoma with or without DCIS) who had an oriented lumpectomy specimen and also had four to six additional CMs. The tumors were evaluated for the following: size, grade, LM status (distance of tumor from margin and, if involved, extent of involvement), vascular invasion, lymph node status, and presence or absence of extensive intraductal component. The additional CM specimens were evaluated for residual carcinoma (if any) and its distance from the inked true margins, and the results were correlated with the corresponding LMs. Only approximately 50% of patients (52 of 103) with histologically positive LMs (defined as carcinoma within 2 mm of the inked surface) had residual carcinoma in their CMs. Additional CM sampling rendered the overall final margin status histologically negative in 61 of 103 (59%) cases with histologically positive LMs, therefore significantly reducing the need for reexcision. Younger patient age, higher number of positive LMs, high tumor grade, and the presence of extensive intraductal component were predictive of residual carcinoma in CM specimens, whereas the distance of carcinoma from the inked surface and the extent of tumor involvement of histologically positive LMs were not. Because CM specimens taken from patients with histologically positive LMs usually lack tumor, we suspect that many positive LMs are likely false positives. Possible factors accounting for false-positive LMs include seepage of ink into crevices of the specimen promoted by excessive inking, tumor friability promoting displacement of tumor into ink, manipulation of specimens for radiographs, and retraction artifact.