The epididymal fat pad as a transplant site for minimal islet mass

The epididymal fat pad was evaluated as a site of islet transplantation in a syngeneic murine model of diabetes by comparing the transplant outcomes to that of islets transplanted intraportal. Mouse islets engrafted on the intra-abdominal epididymal fat pad ameliorated streptozotocin-induced hyperglycemia with similar efficacy as grafts implanted intraportally. Mice that received as few as 50 islets, either intraportal or in the epididymal fat pad, displayed similar glucose tolerance curves. Bioluminescence imaging and glucose measurement showed stable luminescence signals and blood glucose levels for over 5 months in both transplant sites using transgenic luciferase-positive islets. Prompt recurrent hyperglycemia occurred in all mice after removal of the epididymal fat pad bearing the islet graft. Histological examination of the grafts showed well-granulated insulin containing cells surrounded by healthy adipocytes. This study indicates that the epididymal fat pad maybe a useful islet transplant site in the mouse model for effective glycemic control.     

Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis

Carpal tunnel syndrome (CTS) is a peripheral neuropathy characterized by non‐inflammatory fibrosis of the subsynovial connective tissues (SSCT). A rabbit model of CTS was developed to test the hypothesis that SSCT fibrosis causes the neuropathy. We used a cell‐seeded collagen‐gel contraction model to characterize the fibrosis in this model in terms of cellular mechanics, specifically to compare the ability of SSCT cells from the rabbit model and normal rabbits to contract the gel, and to assess the effect of transforming growth factor‐β1,which is upregulated in CTS, on these cells. SSCT fibrosis was induced in six retired breeder female rabbits which were sacrificed at 6 weeks (N = 3) and 12 weeks (n = 3). An additional two rabbits served as controls. SSCT was harvested according to a standard protocol. Gels seeded with SSCT cells from rabbits sacrificed at 6 weeks had significantly higher tensile strength (p < 0.001) and Young's modulus (p < 0.001) than gels seeded with cells from rabbits sacrificed at 12 weeks or control animals. TGF‐β1 significantly increased the decay time constant (p < 0.001), tensile strength (p < 0.001), and Young's modulus (p < 0.001) regardless of the cell source. This model may be useful in screening therapeutic agents that may block SSCT fibrosis, identifying possible candidates for CTS treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:668–674, 2015.     

18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Scanning Affects Surgical Management in Selected Patients With High-Risk, Operable Breast Carcinoma

Background The role of positron emission tomography (PET) scanning in determining the extent of disease in patients with breast cancer has not been defined. We investigated the utility of ¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk, operable breast cancer. Methods This was a prospective study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer. Eighty eligible patients were enrolled and underwent computed tomographic chest, abdomen, pelvis, and bone scans, followed by FDG-PET. Changes in treatment based on scan findings were recorded by the operating surgeons. Imaging findings were verified by biopsy or long-term follow-up. Results Eight (10%) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET. Four additional patients (5%) had additional foci of disease on PET that affected treatment decisions. No patient had findings on conventional imaging alone. Conventional imaging studies resulted in a higher number of findings that generated additional tests and biopsies that ultimately had negative results (17% vs. 5% for PET). There was a statistically significant difference in specificity for PET compared with conventional imaging (P = .01). Conclusions Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk, operable breast cancer, but PET generated fewer false-positive results. FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer.     

Incidental focal thyroid uptake on FDG positron emission tomographic scans may represent a second primary tumor

PURPOSE: This article discusses the value of incidental thyroid uptake of fluorodeoxyglucose (FDG) on whole-body positron emission tomography (PET) scans performed in patients with cancer. This issue has been reported diversely in the literature. MATERIALS AND METHODS: Whole-body PET scans of four patients with cancer (two of them women; age, 49 to 78 years) in whom focal thyroid uptake was visualized and subsequently correlated with thyroid carcinoma based on cytologic or histopathologic data were reviewed. The clinical outcomes of these patients were analyzed retrospectively. Maximum and average standardized uptake values (SUVs) of thyroid accumulation were recalculated in all patients. RESULTS: Two of the four patients referred for FDG PET scans had lung adenocarcinomas, one had prostate carcinoma, and one had an unknown primary tumor. Focal thyroid uptake was visualized, with maximum and average SUVs ranging from 3.7 and 2.3 to 53 and 34, respectively. These findings were correlated with cytologic (two patients) or histopathologic data (two patients) that indicated thyroid carcinoma. In two patients, their treatment was changed and total thyroidectomy was performed; in one of them the SUVs of the focal thyroid accumulation (maximum and average values of 7.9 and 4.8, respectively) were less than the cutoff values for thyroid cancer noted in the literature. The clinical condition of the other two patients did not permit additional investigation or treatment for thyroid carcinoma. CONCLUSION: Increased focal thyroid uptake on whole-body FDG PET scans should not be overlooked, even when it is not marked, and should prompt further investigation to rule out cancer.     

Chromatin structure in globozoospermia: a case report

Sperm nuclear abnormalities in patients with globozoospermia have not been well characterized and may lead to the high rates of fertilization failure and embryo loss reported in patients with this form of teratozoospermia. This study used transmission electron microscopy (TEM), the sperm chromatin structure assay (SCSA), and single cell gel eletrophoresis assay (COMET) to assess if globozoospermia is associated with sperm chromatin structure abnormalities, DNA fragmentation, or both. The flow cytometric SCSA measures abnormal chromatin structure based on the susceptibility of sperm nuclear DNA to acid-induced denaturation in situ. COMET measures DNA fragmentation in individual sperm nuclei based upon gel electrophoretic patterns. Although sperm concentration (113 million/mL) and motility (66%) were normal in the patient, there was complete acrosome deficiency. TEM and SCSA data confirmed light microscopic examination that showed that sperm populations included a mixture of round and elongated sperm heads. Even though 100% of sperm had abnormal head morphology, only 13% demonstrated DNA denaturation (COMPalpha(t)), which is below our threshold of 15% COMPalpha(t), and consistent with high-fertility patients. Of interest, 13% of the sperm were also positive in the COMET assay, supporting our previous observations that SCSA-positive cells are also positive for DNA fragmentation. It was unexpected but of great interest that a human sperm population with 100% sperm morphology abnormalities had a chromatin integrity at the molecular level that is equivalent to sperm populations shown in previous studies to be highly fertile. These data are the first reported using SCSA and COMET assays to evaluate a patient with globozoospermia and support previous reports that intracytoplasmic sperm injection of globozoospermia may result in fertility/pregnancy. Lower success rates seen in some patients may be due to unrelated factors.     

One-peg versus three-peg patella component fixation in total knee arthroplasty.

In many designs of total knee arthroplasty, the patella with one central peg has been replaced by a patella with three small pegs for cement fixation. There have been recent reports of failure of this design. This is a prospective, consecutive study of two types of patella component fixation in 228 posterior-stabilized knee arthroplasties done by one surgeon. A central peg all-polyethylene component was used for 84 consecutive knees in 63 patients (Group A) and a three-peg patella was used for the next 144 consecutive knees in 99 patients (Group B). The mean followup was 6.7 years (range, 2-10 years) for Group A and 3.5 years (range, 2-6 years) for Group B. Except for the patellar component fixation, all knees had the same posterior-stabilized prosthesis using a specific protocol for patellar resurfacing. No patient required reoperation for a patellofemoral complication. The prevalence of patella fracture was higher in Group A, 4.7% (four knees), compared with 2.1% (three knees) in Group B, but this difference was not statistically significant. The presence of anterior knee pain referable to the patella was 7.1% (five patients, six knees) in Group A (one patient with two knees had severe anterior knee pain) and 9% (13 knees in 13 patients) in Group B. There was no patella clunk syndrome, subluxation, or fracture of a fixation peg in either group. With this specific protocol for patella resurfacing, there was a higher rate of complications with the one central peg patella (4.7%) than with the three-peg patella (2.1%), but this did not reach statistical significance. The results do not support an increased risk of component failure with this three-peg patella design, but do not, at this length of followup, show any significant advantage of three-peg fixation.     

An assay of the toxicity of the Atlantic puffer fish, Spheroides maculatus

Skin, muscle, liver, and gonadal extracts of the Atlantic puffer, Spheroides maculatus were assayed for toxicity in white mice. Extracts were injected intraperitoneally and were administered in the amounts of 1 ml per 20 g of body weight. The LD₅₀ of a composite skin extract, administered intraperitoneally in progressive doses per 20 g of body weight, was determined for white rats, white mice, chicks and frogs (Rana pipiens), while a LD₅₀ of a composite muscle extract was determined for the pinfish, Lagodon rhomboides.     

Long-term outcomes of vitrectomy with or without arteriovenous sheathotomy in branch retinal vein occlusion

PURPOSE: To evaluate the long-term effect of vitrectomy with or without arteriovenous sheathotomy for macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: The study was a prospective, randomized, comparative, interventional case series of 36 patients (36 eyes) who underwent pars plana vitrectomy with or without arteriovenous sheathotomy for macular edema due to BRVO of 相似文献   

Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.