Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification. Report of two cases

The authors report on two gonadotropic carcinomas of the adenohypophysis that occurred in a55-year-old man (Case 1) and a 53-year-old woman (Case 2), with signs of mass effect and amenorrhea, respectively. Both lesions were macroadenomas. The tumor in Case 1 metastasized to dura mater, skull, nasal sinus, and larynx 2 years after patient presentation, whereas that in Case 2 spread to vertebral bodies and ribs after a 19-year latency. Histologically, the primary, recurrent, and metastatic lesions in Case 1 featured brisk mitotic activity and high MIB-1 levels as well as p53 labeling indices. Immunoreactivity for HER-2/neu was assessable only in rare neoplastic cells of the second recurrence and in 80% of cells of the dural metastasis. Low-level HER-2/neu gene amplification was evident in the recurrent tumors and metastasis. The sellar and metastatic tumors in Case 2 resembled benign gonadotropic adenoma with oncocytic change; p53 accumulation, HER-2/neu overexpression, and HER-2/neu gene amplification were not present. The results indicate that low-level amplification of the HER-2/neu gene might be associated with pituitary carcinomas in which more aggressive behavior is seen. Further studies are needed to determine whether HER-2/neu plays a role in the pathogenesis of pituitary carcinoma.     

Fluoropolymer coated Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicentre trial

Background: This trial was designed to compare graft patency between expanded polytetrafluoroethylene (PTFE) and fluoro­polymer coated Dacron for femoropopliteal bypass in patients in whom saphenous vein was unavailable. Methods: A multicentre prospective trial randomized 129 patients (74 men, 55 women) who underwent femoropopliteal bypass using either a PTFE or fluoropolymer coated Dacron graft. The indication for operation was disabling claudication in 68 (52.7%) and critical limb ischaemia in 61 (47.3%) patients. Distal anastomosis was above the knee in 76 (58.9%) and below the knee in 53 (41.1%) patients. Results: Primary patency at 6, 12 and 24 months was 71%, 56% and 47% for PTFE and 50%, 36% and 36% for fluoropolymer coated Dacron (P = 0.002), respectively. Secondary patency at 6, 12 and 24 months was 77%, 60% and 48% for PTFE and 66%, 49% and 46% for fluoropolymer coated Dacron (P = 0.13), respectively. The superior primary patency of PTFE over fluoropolymer coated Dacron was most evident in patients with poor prognostic indicators for graft survival: critical limb ischaemia (P = 0.001); below‐knee anastomosis (P = 0.01); and smaller (6 mm) diameter grafts (P = 0.002). Graft thrombosis developed in the first month in 22 of 61 (36%) patients receiving fluoropolymer coated grafts compared to six of 68 (8.8%) patients receiving PTFE, which accounts for the difference in primary patency. Successful thrombectomy in 10 of the 22 fluoropolymer coated grafts resulted in similar secondary patency. Conclusion: Polytetrafluoroethylene has superior primary patency and similar secondary patency to fluoropolymer coated Dacron. These results support the preferential use of PTFE in patients with critical limb ischaemia, especially when a below‐knee distal anastomosis and smaller diameter graft is required.     

New methodology for assessment of intimal hyperplasia of vascular prostheses

Background: When investigating the degree of formation of intimal hyperplasia (IH) quantification of the extent of the lesion is crucial to its assessment and analysis. The aim of the present study was to establish a new methodology (IH index) for estimating the degree of IH associated with vascular prosthesis implantation. Methods: Ten female Merino sheep underwent a standard gelatin sealed Dacron (GSD) patch grafting procedure in the left common carotid artery. The grafts were harvested 4 weeks following implantation and processed for assessment of IH by two methodologies ? mean intimal thickness (MIT) and IH index. The advantages and disadvantages of the two methods for expressing the degree of IH were compared. Results: The IH index is less labour intensive but is as accurate as the MIT method in quantifying the IH lesion, statistical analysis showing high correlation and measurement agreement between the two methods. Conclusion: The IH index is a labour saving standardized methodology for quantification of IH in the current animal model.     

Ultrahigh dose gentamicin alters inflammation and angiogenesis in vivo and in vitro

Skin quality outcome after skin grafting is adversely affected by wound bed inflammation. Neomycin, gentamicin, and other aminoglycoside antibiotics are known to modulate inflammation, and topical application affords the use of higher doses than are possible to use systemically. Previous data suggest that clinically relevant doses of neomycin, but not gentamicin, may impair angiogenesis, which is critical to the durable survival of skin grafts. The role of gentamicin at ultrahigh doses compared with clinically relevant neomycin doses in regulating inflammatory expression and angiogenesis has been examined. In a porcine skin replacement excisional wound model, continuous exposure to gentamicin increased anti‐angiogenic and inflammatory expression at 7 days postgrafting. In in vitro studies, gentamicin also impaired angiogenesis in a human umbilical vein endothelial cell (HUVEC) tube formation model, increased the expression of the anti‐angiogenic gene C‐X‐C motif chemokine 10 (CXCL10) in HUVECs and macrophages, and increased pro‐inflammatory cytokine expression of macrophages in a dose‐dependent manner. Neomycin exerted similar effects in vitro at clinically relevant doses on HUVEC tube formation and macrophage pro‐inflammatory expression. CXCL10 was upregulated in macrophages, but did not exhibit a change in HUVECs with neomycin treatment. Ultrahigh doses of gentamicin and clinically relevant doses of neomycin affect inflammation and angiogenesis in in vivo and in vitro models. These findings suggest that topical administration of aminoglycosides have the potential to adversely influence early skin graft survival.     

Chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the leading cause of renal allograft loss in paediatric renal transplant recipients. CAN is the result of immunological and nonimmunological injury, including acute rejection episodes, hypoperfusion, ischaemia reperfusion, calcineurin toxicity, infection and recurrent disease. The development of CAN is often insidious and may be preceded by subclinical rejection in a well-functioning allograft. Classification of CAN is histological using the Banff classification of renal allograft pathology with classic findings of interstitial fibrosis, tubular atrophy, glomerulosclerosis, fibrointimal hyperplasia and arteriolar hyalinosis. Although improvement in immunosuppression has led to greater 1-year graft survival rates, chronic graft loss remains relatively unchanged and opportunistic infectious complications remain a problem. Protocol biopsy monitoring is not current practice in paediatric transplantation for CAN monitoring but may have a place if new treatment options become available. Newer immunosuppression regimens, closer monitoring of the renal allograft and management of subclinical rejection may lead to reduced immune injury leading to CAN in the paediatric population but must be weighed against the risk of increased immunosuppression and calcineurin inhibitor nephrotoxicity.     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.     

The National Health and Medical Research Council Road Map: a strategic framework for improving Aboriginal and Torres Strait Islander health through research

What impact has the NHMRC Road Map had on Aboriginal and Torres Strait Islander health? A review process now underway aims to find out.     

Primary hepatic angiosarcoma: findings at CT and MR imaging

PURPOSE: To evaluate and describe cross-sectional imaging findings in patients with pathologically confirmed primary hepatic angiosarcoma. MATERIALS AND METHODS: Findings from imaging examinations in 13 patients with pathologically confirmed primary hepatic angiosarcoma were retrospectively reviewed (computed tomographic [CT] images obtained in 10 patients and magnetic resonance [MR] images obtained in five patients were available for review). Two gastrointestinal radiologists evaluated lesion number, size, attenuation and signal intensity characteristics, and the pattern and degree of contrast material enhancement. Medical records were reviewed for clinical features associated with angiosarcoma. RESULTS: Angiosarcoma appeared as multiple nodules (n = 6), as dominant masses (n = 6), or as a diffusely infiltrating lesion (n = 1). Multiple nodules were hypoattenuating at unenhanced and contrast material--enhanced CT (six of six patients). When dominant masses were encountered at MR imaging, T2-weighted MR imaging demonstrated heterogeneous internal architecture (four of four patients) similar to that of hepatocellular carcinoma. Multiphase contrast-enhanced CT and MR images showed dominant masses to have heterogeneous and progressive enhancement (three of three patients). Clinical features associated with angiosarcoma included splenic metastases (six of 13 patients), thrombocytopenia (seven of 13 patients), disseminated intravascular coagulation (four of 13 patients), and hemolytic anemia (three of 13 patients). CONCLUSION: Primary hepatic angiosarcoma exhibits a spectrum of appearances that reflect its varied pathologic features.     

Deep fungal and higher bacterial skin infections in Thailand: clinical manifestations and treatment regimens

BACKGROUND: Deep fungal and higher bacterial skin infections occur fairly frequently in Thailand. METHODS: Cases with a provisional diagnosis of deep fungal and higher bacterial infections were prospectively collected from 1994 to 1997 in the Granuloma Clinic, Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Demographic data, clinical manifestations, causative organisms, histologic features, treatment, and outcome were investigated. RESULTS: The total cases in a 4-year period numbered 27. The male to female ratio was approximately 1:1. Mycetoma was most common, followed by chromoblastomycosis. Actinomycetoma was similar in incidence to eumycetoma. The only causative organism that could be identified among the mycetoma cases was Cladosporium carrionii, which caused mycetoma of the buttock of an aplastic anemia patient at the site of bone marrow aspiration. Surgical treatment was recommended for eumycetoma. Chromoblastomycosis was caused by C. carrionii and F. compactum and responded well with itraconazole orally. Mycotic abscesses were found in four cases, basidiobolomycosis in two cases, and cutaneous nocardiosis in one case. Cotrimoxazole was recommended in the treatment of actinomycetoma, cutaneous nocardiosis, and basidiobolomycosis. CONCLUSIONS: Localized, chronic, slow, progressive, and usually asymptomatic were the main cutaneous manifestations of deep fungal and higher bacterial skin infections. A skin biopsy for histologic study and culture identification should be performed in every suspected case. The causative organisms were found in the histologic sections of every case, but only about one-third were found by culture.     

Catheter ablation of hemodynamically compromising incessant atrioventricular tachycardia.

A 27-year-old woman was admitted to the Georgetown University Hospital with refractory hemodynamically compromising incessant atrioventricular tachycardia. A single left-sided accessory pathway was identified and successfully modified acutely. Endocardial delivery of direct current energy provided an extremely effective therapeutic intervention resulting in termination of atrioventricular tachycardia and restoration of stable hemodynamic status. Although a second ablation procedure was necessary to permanently interrupt accessory pathway conduction, the patient has remained free of symptoms without medications for 13 months.