The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage

OBJECTIVE: Cartilage swelling is an early event in osteoarthritis (OA). However, the response of chondrocytes to increased tissue hydration is unknown. This work studied the volume and morphology of living in situ human chondrocytes as a function of cartilage degeneration. METHODS: The tibial plateaus from knee joints of 40 patients were obtained following above-knee amputations or knee arthroplasty, and degree of cartilage degeneration from 0 (non-eroded) to 3 (extensive fibrillations) was assessed using several criteria. In situ chondrocytes were labeled with fluorescent indicators (calcein for living cells, propidium iodide for dead cells) permitting the quantification of volume and visualisation of morphology of cells within the cartilage zones by confocal scanning laser microscopy (CLSM). RESULTS: Chondrocyte volume within superficial and mid-zones, but not of deep zone cells, increased significantly (P<0.05 and P<0.02, respectively; one-way analysis of variance), with degree of cartilage hydration and degeneration. The volume increase ( approximately 90% for mid-zone chondrocytes, grade 3 cartilage) was greater than that which might occur following loss/excision of sub-chondral bone (<15% swelling). The CLSM technique utilised here revealed that approximately 40% of chondrocytes within all cartilage grades exhibited at least one cytoplasmic processes of <8 microm. The presence of these processes did not indicate a cell body of larger volume than cells without processes, and did not contribute to cell volume. CONCLUSIONS: The volume of in situ chondrocytes within the superficial and mid-zones increased with cartilage degeneration. Cell swelling was greater than that expected from the increased hydration in OA, suggesting that an increase in chondrocyte volume might play a role in the changes to matrix metabolism occurring in OA.     

Impact of an endovascular program on the operative experience of abdominal aortic aneurysm in vascular fellowship and general surgery residency

BACKGROUND: This study was performed to determine the impact of an endovascular program (EVP) on open and endovascular abdominal aortic aneurysm (AAA) operations in a residency training institution. METHODS: Over an 8-year period ending in September 2001, hospital records of all patients undergoing open or endovascular AAA repair were retrospectively reviewed. Data were analyzed to determine the changing patterns of case volume, type of operative repair, and complexity of open repair with regards to the training of both general surgical chief residents and vascular fellows. RESULTS: A total of 849 AAA operations were performed during the study period. The initiation of the EVP in 1997 resulted in a steady increase in the total annual AAA cases (P < 0.05), due in part to an increase in endovascular AAA operations despite a decrease in the annual open AAA volume. EVP had a positive impact on the overall operative experience of vascular fellows owing to the large increase in their endovascular AAA experience (annual mean pre-EVP 3 +/- 0.8 versus post-EVP 47 +/- 9.6, P < 0.01). A significant reduction occurred in the vascular fellows' open AAA experience (annual mean pre-EVP 40 +/- 12.7 versus post-EVP 19 +/- 9.4, P < 0.05). EVP did not affect the endovascular AAA experience of general surgery chief residents (annual mean pre-EVP 1 +/- 0.8 versus post-EVP 3 +/- 1.5, not significant). A significant reduction occurred in chief residents' open AAA experience (annual mean pre-EVP 39 +/- 9.7 versus post-EVP 18 +/- 7.4, P < 0.05). EVP did not affect the operative experience of complex open AAA operations in either vascular fellows or general surgery residents. CONCLUSIONS: An endovascular program has a positive impact on the aortic aneurysm practice in an academic institution, as evidenced by the significant increase in annual endovascular AAA cases despite a decrease in open AAA operations. Although vascular fellows continued to maintain sufficient experience in both open and endovascular AAA operations, general surgery chief residents suffered a significant decrease in their open AAA experience. Further evaluation of the residency system is warranted to better optimize the training paradigm of both vascular fellowship and general surgery residency.     

Risk Factors for De Novo Malignancy Following Lung Transplantation

Risk factors for non–skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow‐up time was 1086 days (interquartile range 436–2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95–3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04–8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45–22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02–1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02–1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37–0.97, p = 0.04) and single‐lung transplantation (HR 1.64, 95% CI: 1.34–2.01, p < 0.001). Significant interactions between donor or recipient smoking and single‐lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10–1.88, p = 0.009).     

Retrospective Study on Fatal Melioidosis in Captive Zoo Animals in Thailand

Melioidosis is caused by Burkholderia pseudomallei and is an important zoonotic infectious disease causing high mortality from fulminant septicaemia in humans and a wide variety of animal species. The incidence of fatal melioidosis in zoo animals has been significant in many Thai zoos. A total number of 32 cases were evaluated throughout the Thai zoo animal populations. The highest prevalence of disease has been reported from the north‐eastern region followed by the zoos in the southern part of the country, approximately 47% and 38%, respectively, while the other zoos reported sporadic infections. Herbivores and non‐human primates were the most commonly affected animals with incidences of 59% and 28%, respectively. This appears to be a seasonal correlation with the highest incidence of melioidosis in zoo animals reported in the rainy season (44%) or subdivided monthly in June (19%) followed by September and November (16% and 12%, respectively). The route of infection and the incubation period still remain unclear. This retrospective study examined the clinical presentation in various zoo species, pathological findings and epidemiological data as well as conducting an in depth literature review.     

Absorbable cyanoacrylate as a vascular hemostatic sealant: a preliminary trial

No absorbable cyanoacrylate tissue adhesive for safe internal surgical use is available. This prospective multicenter preliminary study was designed to evaluate the safety and effectiveness of an investigational absorbable cyanoacrylate (IAC) as an adjunct to hemostasis in arteriovenous shunt (AVS) procedures for dialysis access. Consenting adults (10) underwent placement of expanded polytetrafluoroethylene (ePTFE) upper extremity vascular grafts for AVS access using continuous 5-0 or 6-0 polypropylene after heparinization (> or =3000 units i.v.). Arterial anastomoses were evaluated after sealing with IAC followed by 120 seconds of polymerization time. After vascular clamp removal, the mean time to hemostasis was 9.1 +/- 28.8 seconds. Additionally, 90 per cent (9/10) and 100 per cent (10/10) achieved hemostasis by 1 and 5 minutes, respectively. No patients required further adjunctive hemostatic measures. Adverse event safety data analysis through 12 weeks revealed occlusion of graft or vessel in four patients and graft thrombosis in one patient, all thought unrelated to sealant use. Other unrelated adverse events (bleeding, death, deep venous thrombosis, edema, erythema, hematoma, infection, and rash) occurred in single patients. Thus, IAC could be a useful sealant for vascular procedures with a potentially satisfactory safety profile. Larger, randomized, multicenter, prospective trials to further evaluate the use of this material are indicated and appropriate.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl- phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK- 74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.     

Hydrogen peroxide contrast echocardiography

Several agents are used as echocardiographic contrast agents, but their unreliability discourages routine clinical use. Studies from the early 1960s suggest that dilute hydrogen peroxide (H₂O₂) is a safe intravascular agent. Its use was evaluated in contrast echocardiography. To obtain dense opacification reliably, H₂O₂ (3%) was passed through a sterile 0.2 μ Millipore filter and diluted with heparinized saline solution to make a 0.1 to 0.2% solution. A drop of blood was withdrawn from an indwelling peripheral venous needle into a syringe containing 0.5 to 2.0 ml of the dilute H₂O₂ and the contents injected. Studies in dogs, normal adults and 36 patients with noncyanotic congenital and acquired cardiac disorders produced dense opacification with no complications. In vitro mixture of H₂O₂ (0.3%) with leukocyte-poor blood or plasma produced only a few microbubbles, while addition to whole blood or buffy coat produced many, suggesting a role for leukocyte peroxidase. H₂O₂ contrast echocardiography is simple, inexpensive, and reliably provides dense, sustained opacification. This study and previous studies suggest that intravenous injection of 0.2% H₂O₂ can be done safely. Great caution should be exercised in patients with severe pulmonary hypertension or large right-to-left shunts because little clinical experience with H₂O₂ is available.