Tailoring nanostructure and bioactivity of 3D-printable hydrogels with self-assemble peptides amphiphile (PA) for promoting bile duct formation.

3D-printing has expanded our ability to produce reproducible and more complex scaffold architectures for tissue engineering applications. In order to enhance the biological response within these 3D-printed scaffolds incorporating nanostructural features and/or specific biological signaling may be an effective means to optimize tissue regeneration. Peptides amphiphiles (PAs) are a versatile supramolecular biomaterial with tailorable nanostructural and biochemical features. PAs are widely used in tissue engineering applications such as angiogenesis, neurogenesis, and bone regeneration. Thus, the addition of PAs is a potential solution that can greatly expand the utility of 3D bioprinting hydrogels in the field of regenerative medicine. In this paper, we firstly developed a 3D-printable thiolated-gelatin bioink supplemented with PAs to tailor the bioactivity and nanostructure which allows for the incorporation of cells. The bioink can be printed at 4 °C and stabilized to last a long time (>1 month) in culture at 37 °C by via a dual secondary crosslinking strategy using calcium ions and homobifunctional maleiminde-poly (ethylene glycol). Rheological properties of inks were characterized and were suitable for printing multi-layered structures. We additionally demonstrated enhanced functionality of ink formulations by utilizing a laminin-mimetic IKVAV-based PA system within a 3D-printable ink containing cholangiocytes. Viability and functional staining showed that the IKVAV PA nanofibers stimulated cholangioctyes to form functional tubular structures, which was not observed in other ink formulations.

3D-printing porosity: A new approach to creating elevated porosity materials and structures.

We introduce a new process that enables the ability to 3D-print high porosity materials and structures by combining the newly introduced 3D-Painting process with traditional salt-leaching. The synthesis and resulting properties of three 3D-printable inks comprised of varying volume ratios (25:75, 50:50, 70:30) of CuSO4 salt and polylactide-co-glycolide (PLGA), as well as their as-printed and salt-leached counterparts, are discussed. The resulting materials are comprised entirely of PLGA (F-PLGA), but exhibit porosities proportional to the original CuSO4 content. The three distinct F-PLGA materials exhibit average porosities of 66.6-94.4%, elastic moduli of 112.6-2.7 MPa, and absorbency of 195.7-742.2%. Studies with adult human mesenchymal stem cells (hMSCs) demonstrated that elevated porosity substantially promotes cell adhesion, viability, and proliferation. F-PLGA can also act as carriers for weak, naturally or synthetically-derived hydrogels. Finally, we show that this process can be extended to other materials including graphene, metals, and ceramics. STATEMENT OF SIGNIFICANCE: Porosity plays an essential role in the performance and function of biomaterials, tissue engineering, and clinical medicine. For the same material chemistry, the level of porosity can dictate if it is cell, tissue, or organ friendly; with low porosity materials being far less favorable than high porosity materials. Despite its importance, it has been difficult to create three-dimensionally printed structures that are comprised of materials that have extremely high levels of internal porosity yet are surgically friendly (able to handle and utilize during surgical operations). In this work, we extend a new materials-centric approach to 3D-printing, 3D-Painting, to 3D-printing structures made almost entirely out of water-soluble salt. The structures are then washed in a specific way that not only extracts the salt but causes the structures to increase in size. With the salt removed, the resulting medical polymer structures are almost entirely porous and contain very little solid material, but the maintain their 3D-printed form and are highly compatible with adult human stem cells, are mechanically robust enough to use in surgical manipulations, and can be filled with and act as carriers for biologically active liquids and gels. We can also extend this process to three-dimensionally printing other porous materials, such as graphene, metals, and even ceramics.

Arthrofibrosis following total knee replacement; does therapeutic warfarin make a difference?

Arthrofibrosis following total knee replacement (TKR) is a relatively common complication which results in a reduction in knee range of movement and patient dissatisfaction. A retrospective study examined the relationship between anticoagulation with therapeutic warfarin and rates of arthrofibrosis following TKR. Arthrofibrosis was defined as less than 80 degrees of knee flexion 6-8 weeks post-TKR. Patients were warfarinised if they had a history of thrombophilic tendencies or medical conditions necessitating anti-coagulation, rather than as routine thromboprophylaxis. All other patients received thromboprophylaxis using low molecular weight heparin. A total of 728 patients underwent 874 primary TKR between 1993 and 2002 in one centre, performed by four surgeons. Mean age was 68 years (range 48-89 years) and there were 483 female and 391 male knees. Eighty cases were warfarinised post-operatively (53 female, 27 male). Overall, 83 of 874 TKRs (9%) had arthrofibrosis (57 female, 26 male) requiring manipulation under anaesthetic (MUA). In the warfarinised group, 21 knees (26%) had an MUA (15 female, 6 male). This compared to 62 cases (8%) requiring MUA in the non-warfarinised group (42 female, 20 male). There was a statistically significant difference on Fisher's exact testing (P<0.0001) between groups. Following MUA, knee flexion improved in 95% cases to a minimum 95 degrees but 8 cases had a fixed flexion deformity of 5-10 degrees . In conclusion, therapeutic warfarinisation post-TKR leads to a statistically greater chance of the patient developing arthrofibrosis compared to prophylactic low molecular weight heparin and that patients should be counseled appropriately.

Dexamethasone stimulation of fetal rat lung antioxidant enzyme activity in parallel with surfactant stimulation.

It has recently been determined that fetal lung antioxidant enzyme activity markedly increases late in gestation. A test was made of whether this normal late-in-gestation change in O2-protective enzymes would be responsive to the maturing effect of hormonal (glucocorticoid) treatment. Pregnant rats received 0.2 mg/kg of dexamethasone (or saline) at 48 and 24 hours prior to delivery of their fetuses on gestational days 19, 20, 21, and 22 (newborn). Lung disaturated phosphatidylcholine showed an expected response to prenatal dexamethasone exposure with significant elevations of surfactant lipid at gestational days 20 and 21. A similar effect of prenatal dexamethasone treatment on the lung antioxidant defensive system was found. Superoxide dismutase, catalase, and glutathione peroxidase--enzymes protective against hyperoxia-induced lung injury--showed an accelerated pattern of maturation with significant increases in the dexamethasone-treated fetal lungs compared with control fetal lung enzyme levels at gestational days 20 and 21. The results suggest that prenatal dexamethasone treatment may have dual benefits when used in impending premature deliveries--that is, it may stimulate maturation of both the surfactant system and also the antioxidant enzyme system, and this maturation can help protect the premature newborn's lungs from the toxic complications of hyperoxic therapy that may be required because of immaturity.

Is the quality of surgical residency applicants deteriorating?

BACKGROUND: Among directors of general surgery residencies, there is a concern that the quality of medical students applying to surgical residencies is declining. METHODS: Quality of surgical applicants was assessed by several methods including subjective opinions determined by survey and by objective data including student United States Medical Licensing Examination (USMLE) scores of matched candidates. The number of applicants interviewed, total interviews granted, proportion of Alpha Omega Alpha (AOA) students, and the rank order of the candidates matched was obtained by survey. The survey included data on postgraduate year 1 (PGY-1) residents from July 1996 to July 1999. Three mailings were made to 226 US surgical residency programs. RESULTS: Data were obtained from 90 programs. Surgery program directors disagreed with a survey statement that overall quality of applicants had declined (P <0.01), but agreed with a statement that activities of medical schools to enroll graduating students into primary care had hurt recruitment (P <0.001). Objective data revealed no change in mean USMLE part I scores of PGY-1 residents over the 4 years (P = 0.265, power = 0.81). There was no change in proportion of matched residents who were AOA over time. The mean score of all new PGY-1 residents, the rank of the first matched resident, the rank of the last ranked resident, and proportion of AOA students was higher in programs with five or more categorical spots when compared with programs of at most four (P <0.001). Across all programs, there was a trend to go lower on the rank list to fill categorical positions over time (P <0.001). CONCLUSIONS: There is a perception that medical school policies act to discourage recruitment of quality medical students into general surgery programs, and surgery programs are going deeper into their rank lists to fill categorical positions. However, the average USMLE part I score of applicants to surgical residencies and proportion of AOA applicants has not decreased.

The Miller-Galante knee prosthesis for the treatment of osteoarthrosis. A comparison of the results of partial fixation with cement and fixation without any cement.

In a prospective, non-randomized study of 344 patients who had 392 primary total knee replacements with a Miller-Galante I prosthesis for the treatment of osteoarthrosis, the results of partial fixation with cement (insertion of the tibial and patellar components with cement and of the femoral component without cement) were compared with those of fixation without any cement. Of the 392 knees, 183 (163 patients) had fixation without cement (Group I) and 209 (181 patients), with and without cement (Group II). The average duration of follow-up was three years (range, two to five years). Nine patients died during the follow-up period, but no others were lost to follow-up. Analysis of the knee scores, range of motion of the knee, radiographs, and rates of complications revealed no differences between the outcomes in the two groups during the follow-up period. The rate of complications due to problems related to the extensor mechanism was high in both groups: a reoperation was performed in fifteen (8 per cent) of the knees that had had fixation without cement and in nineteen (9 per cent) of those that had had both types of fixation. Thirteen patients had additional operative treatment for recurrent patellar dislocations; twelve patients, for abnormal wear of the polyethylene of the patellar component: two patients, for avulsion of the patellar ligament from the tibia; and two patients, for unexplained pain in the knee. In addition, there were eight patellar fractures (two of which led to a reoperation) and three deep infections (all of which led to a reoperation).

Biorhythms and tests of oral skills.

The null hypothesis that there is no difference in an individual's level of skill on critical and non-critical days of the biorhythm cycle is tested over a 2-week period using oral stereognosis and a dysarthria assessment. No statistical evidence could be found to refute the null hypothesis proposed and it is concluded that there is no relationship between oral skills and stages of the biorhythm cycle.

The evaluation of subatmospheric pressure and hyperbaric oxygen in ischemic full-thickness wound healing.

We evaluated the efficacy of subatmospheric pressure and hyperbaric oxygen (HBO) as adjuncts in the treatment of hypoxic full-thickness wounds in a rabbit model. We hypothesized that subatmospheric pressure and HBO independently are effective in improving wound healing in the ischemic wound model and that when they are used in combination there is an increased positive effect on wound healing. Using a standard ischemic wound model four full-thickness wounds were created on each ear of 41 male New Zealand white rabbits (N = 82 ears). On each rabbit one ear was dressed with the vacuum-assisted closure (VAC) device and connected to suction; the other was dressed identically without the suction and suction tubing. Twenty rabbits were treated with HBO daily for 10 days at 2.0 atmospheres absolute for 90 minutes plus descent and ascent times. Necropsy on all rabbits was performed on postoperative day 10. Four ischemic wound treatment groups were evaluated: Group 1 (N = 21) VAC dressing alone; Group 2 (N = 20) VAC dressing plus HBO; Group 3 (N = 21) VAC dressing to suction alone; and Group 4 (N = 20) VAC dressing to suction and HBO. Using light microscopy a veterinary pathologist blinded to treatment groups quantified peak granulation tissue, granulation tissue gap, and epithelialization tissue gap. Data were analyzed by analysis of variance with significance indicated by P < 0.05. Statistical significance was found in a comparison of VAC dressing to suction and VAC dressing alone for peak granulation tissue and granulation tissue gap both with and without use of HBO. VAC device use appears to increase the rate of healing in a rabbit ischemic wound model. HBO therapy did not significantly affect the rate of healing in this model.

A long-term review of a modified Evans procedure.

Of 111 primary ankle ligament arthroplasties (modified Evans procedure) performed between 1983 and 1994, we were able to identify 89 patients (94 ankles) for follow-up. All were under 50 years of age. Two had died and one refused to co-operate; 86 patients (91 ankles) were therefore reviewed, 25 by telephone and the remainder by clinical examination with all but three also undergoing radiological review. Of the 91 ankles, 70 had no or very mild pain and 72 had no or rare episodes of instability and when considered together only 59 (65%) had no or mild pain and minimal instability. The results were supported by the Karlsson grading system. Clinical examination showed that 17 of the 66 ankles examined had increased inversion, while 21 had some limitation of inversion. Early degenerative changes were seen in 11 ankles, although only four had subtalar changes. These results show that this procedure does not give universally good clinical results. Patient satisfaction, however, was high with 97.7% being willing to undergo the same procedure if their other ankle became similarly affected.

The pathogenesis of bone loss following total knee arthroplasty.

Bone loss following total knee arthroplasty (TKA) may be focal or diffuse. It may be caused mechanically, either by unloading of the bone leading to disuse osteoporosis, or by overloading of the bone leading to trabecular fractures and bone destruction. Osteolysis, instigated by an inflammatory reaction to particulate wear debris, is an important and common cause of bone loss after TKA. Less common, though sometimes dramatic, causes of bone loss are infection and osteonecrosis.

Heterotopic intrauterine and tubal pregnancy complicated by pulmonary embolism. A case report.

A case of heterotopic pregnancy, an unusual condition in itself, complicated by pulmonary embolus is presented. The patient underwent an elective termination of an intrauterine pregnancy and subsequently was diagnosed with a pulmonary embolus, which delayed the diagnosis of her ruptured ectopic pregnancy.

Gastric remnant cancer after Billroth II procedure.

Six cases of gastric remnant cancer that occurred many years after Billroth II gastrectomy and gastrojejunostomy for benign disease are reported. They are classified as intestinal type and gastric type on the basis of their morphologic appearance. Their cytologic and histologic features are tabulated along with a summary of the clinical histories. Emphasis is placed on the possible high risk for patients with Billroth II procedures of developing cancer 10 to 25 years after surgery. Endoscopic follow-up including cytologic study is essential to diagnose gastric remnant cancer in its early stage to secure a better prognosis.

Two histologic types of early gastric carcinoma and their cytologic presentation.

A study was made of 119 case of early gastric carcinomas as to age, sex, histologic cell types, depth of penetration of the cancer, metastasis to the regional lymph nodes and cellular changes of the mucosa near the foci of center. Two distinctly different cellular types were identified. One was the intestinal type, and the other was a diffusely infiltrated, mixed-cell type that was termed the "gastric" type. In both sexes, the intestinal type occurred in the older age group while the gastric type was noted in the younger age group. Once the cancer had penetrated through the muscularis mucosae, there was a sudden, increased incidence of metastasis to the regional lymph nodes regardless of the cellular type. While still confined to the mucosae, only one case of early gastric carcinoma, one of the gastric type, had metastasized to the regional lymph nodes. On this histologic basis, cytologic characteristics of two types of gastric carcinoma are summarized, and the importance of their recognition is emphasized.

Clinical research during surgery residency: the Chattanooga approach.

PURPOSE: The nontraditional clinical research rotation at the University of Tennessee College of Medicine-Chattanooga Unit is described and its efficacy evaluated by the number of peer-reviewed publications produced. METHODS: In 1988, a mandatory year of clinical research was added to the general surgery curriculum. The year is completed in 3 4-month rotations, 1 each during the PGY-2, PGY-3, and PGY-4 years. Curriculum vitae of 31 graduates of the traditional 5-year residency were evaluated for publications produced during residency and 1 year beyond training. Comparison was made to 15 subjects; 8 were 6-year graduates and 7 were PGY-4, PGY-5, or PGY-6 residents having completed the research year. Statistical analysis used the Mann-Whitney U test for nonparametric data as well as an independent t test with significance set at 0.05. Publications were verified by a MEDLINE search. Six-year graduates also completed a questionnaire regarding their research experience. RESULTS: Graduates of the 5-year program completed an average of 0.94 publications during residency, whereas 6-year graduates completed an average of 2.67 publications (p < 0.001). Opinions varied regarding desire to pursue research and the benefit of the research year. CONCLUSIONS: Our results demonstrate that basic science research is not the only model; academic productivity can be improved with an additional year devoted to clinical research. Advantages to this nontraditional approach include decreased likelihood of decline of clinical skills and knowledge, ability to maintain long-term projects, and a physical and mental break from a demanding clinical residency.

A comparison of cold knife, CO2 laser, and electrosurgical loop conization in the treatment of cervical intraepithelial neoplasia.

Thirty patients with histologically confirmed high-grade squamous intraepithelial lesions (SIL) were treated by either cold knife, laser, or electrosurgical loop conization, all of which were performed under general anesthesia. The three methods were compared with respect to the immediate surgical complications, ease of performance, delayed complications, and quality of histologic specimens. The electrosurgical loop conization had decreased blood loss and reduced operative time and proved to be tissue sparing. There were no significant differences in the three groups in the persistence rates of cervical intraepithelial neoplasia (CN) after treatment. Histologic analysis revealed comparable coagulation artifact in the laser and electrosurgical loop groups that the cold knife group did not have. The endocervical component of the electrocautery showed extensive denudation and coagulation artifact that made recognition of CIN extremely difficult. We conclude that the electrocautery should be used only as an excisional method of the transformation zone for lesions well defined on the ectocervix, since it is unreliable if the lesion extends into the endocervix.

The Unispacer knee implant: early clinical results.

The Unispacer knee system is a cobalt-chrome self-centring tibial hemiarthroplasty device for use in the treatment of isolated medial compartment osteoarthritis of the knee. The indications for use are similar to those for high tibial osteotomy, but insertion does not require bone cuts or component fixation, and does not compromise future knee replacement surgery. A prospective study of a consecutive series of 18 patients treated with the Unispacer between June 2003 and August 2004 was carried out to determine the early clinical results of this device. The mean age of the patients was 49 years (40 to 57). A total of eight patients (44%) required revision within two years. In two patients revision to a larger spacer was required, and in six conversion to either a unicompartmental or total knee replacement was needed. At the most recent review 12 patients (66.7%) had a Unispacer remaining in situ. The mean modified visual analogue score for these patients at a mean follow-up of 19 months (12 to 26) was 3.0 (0 to 11.5). The mean pain level was 30% that of the mean pre-operative level of 10. The early clinical results using this device have been disappointing. This study demonstrates that use of the Unispacer in isolated medial compartment osteoarthritis is associated with a high rate of revision surgery and provides unpredictable relief of pain.

Herbert screw fixation of osteochondral fractures about the knee.

Osteochondral fracture of the patella or femoral condyle may occur with patella dislocation. Accepted treatments of these fractures are excision or replacement. In this paper eight cases are described in which the Herbert Bone Screw system was used for fixation. Normal knee function was regained within 6 months and there were no reported recurrent dislocations. The advantages of this technique are that it is simple, there is little cartilage damage done during insertion, the screw is entirely buried and therefore does not interfere with the soft tissues, fixation is rigid enough to allow for the application of continuous passive motion to aid in cartilage repair, and re-operation for removal is not necessary.