Scaffolds for bone restoration from cuttlefish

Scaffolds of pure hydroxyapatite suitable for either direct clinical use or tissue-engineering applications were successfully produced via hydrothermal transformation of aragonite, obtained from fresh cuttlefish bones, at 200°C followed by sintering. Beyond low production cost, worldwide availability and natural–biological origin of raw materials, the produced scaffolds have ideal pore size and interconnectivity features suitable for supporting biological activities, such as bone tissue growth and vascularization. Bioactivity in vitro tests were excellent: (a) rapid and pronounced formation of hydroxyapatite occurred when the scaffolds were immersed in simulated body fluid (SBF), and (b) outstanding proliferation of osteoblasts was registered. The produced scaffolds can be machined and shaped very easily at any stage of processing. Therefore, these ceramic scaffolds can satisfy both bioactivity demands and the requirements for shaping of tailor-made individualized implants, especially for randomly damaged bones.     

Use of antibiotic cement-impregnated intramedullary nail in treatment of infected non-union of long bones

Background:

In cases with infected non-union, the primary step is eradication of the infection before attempting to achieve union. Release of antibiotics from the bone cement at a high concentration and its penetration to the surrounding tissues, including cortical and cancellous bone, prompted the use of antibiotic cement in the control of bone infection. The aim of this study is to summarize our experience with the use of antibiotic cement-impregnated intramedullary nail (ACIIN) for control of infection in cases of infected non-union with bone defect.

Materials and Methods:

We prospectively studied 25 cases of infected non-union (23 femora and two tibiae). There were 24 males and one female, with the mean age being 33 years (range, 21–58 years). All patients had high-velocity road traffic accidents except one patient who had farmland injury. There were seven closed fractures, one grade I compound, two grade II compound fractures, five grade IIIA compound fractures, and 10 grade IIIB compound fractures. ACIIN was used in all cases after adequate debridement. Patients were classified according to the amount of bone defect present after debridement: group 1 with bone defect <4 cm (n=13), group 2 with bone defect ≥4–<6 cm (n=7), and group 3 with bone defect ≥6 cm (n=5). Infection control was judged on the basis of discharge through the wound and laboratory parameters. All patients were followed-up, with an average follow-up time of 29 months (range, 18–40 months). The mean duration of retention of the intramedullary rod was 8 weeks (range, 6–12 weeks).

Results:

In group 1, all cases achieved infection control, with three patients achieving bone union without any need of secondary procedure. In group 2, all cases achieved infection control but the time taken was significantly longer than for group 1 (P value 0.0002). All the cases required a secondary procedure in the form of either interlocking intramedullary nailing with iliac crest bone graft or Ilizarov ring fixator application to achieve union. None of the cases in group 3 achieved infection control.

Conclusion:

ACIINs are useful for infection control in cases of infected non-union with bone defect <6 cm. In cases with defect >6 cm, other alternatives should be used.     

Kidney Transplantation With Corticosteroid-Free Maintenance Immunosuppression: A Single Center Analysis of Graft and Patient Survivals

The purpose of this study was to assess the impact of a corticosteroid-free maintenance immunosuppression on graft survival in kidney transplantation. We analyzed 79 patients who were transplanted between June 1, 2006 and May 31, 2007. We excluded hyperimmunized patients, second transplantations, living donors, and black recipients. Patients underwent induction with thymoglobulin or basiliximab, followed by treatment with mycophenolate mofetil (MMF), tacrolimus, and methylprednisolone. On the 5th day, the patients were divided into 2 groups: group A (n = 45) discontinued steroid therapy; group B (n = 34) continued prednisone therapy. We performed a comparative analysis of incidence of delayed graft function (DGF), acute rejection episodes (ARE), renal function at 6 and 12 months, graft and patient survivals, causes of graft loss, and mortality. The 2 groups were similar for donor, recipient, and graft characteristics. The incidences of DGF were 8.9% in group A and 14.7% in group B; those for ARE were 2.3% in group A and 13.8% in group B (P = .077). The mean serum creatinine levels at 6 and 12 months were similar. There were 8 graft losses: 3 in group A (3 deaths with functioning grafts) and 5 in group B (1 death, 3 vascular causes, 1 kidney nonfunction). The 4 deaths were due to infection (n = 3) or neoplasia (n = 1). Graft survivals at 1 year were 98% in group A and 85% in group B, and patient survivals were 98% and 97%, respectively. An immunosuppressive regimen using antibody induction and steroid-free treatment proved to be effective in low-risk patients.     

Non-operative management of right side thoracoabdominal penetrating injuries—The value of testing chest tube effluent for bile

Introduction

While mandatory surgery for all thoracoabdominal penetrating injuries is advocated by some, the high rate of unnecessary operations challenges this approach. However, the consequences of intrathoracic bile remains poorly investigated. We sought to evaluate the outcome of patients who underwent non-operative management of right side thoracoabdominal (RST) penetrating trauma, and the levels of bilirubin obtained from those patients’ chest tube effluent.

Patients and methods

We managed non-operatively all stable patients with a single RST penetrating injury. Chest tube effluent samples were obtained six times within (4-8 h; 12-16 h; 20-24 h; 28-32 h; 36-40 h; 48 h and 72 h) of admission for bilirubin measurement and blood for complete blood count, bilirubin, alanine (ALT) and aspartate aminotransferases (AST) assays. For comparison we studied patients with single left thoracic penetrating injury.

Results

Forty-two patients with RST injuries were included. All had liver and lung injuries confirmed by CT scans. Only one patient failed non-operative management. Chest tube bilirubin peaked at 48 h post-trauma (mean 3.3 ± 4.1 mg/dL) and was always higher than both serum bilirubin (p < 0.05) and chest tube effluent from control group (27 patients with left side thoracic trauma). Serum ALT and AST were higher in RST injury patients (p < 0.05). One RST injury patient died of line sepsis.

Conclusion

Non-operative management of RST penetrating trauma appears to be safe. Bile originating from the liver injury reaches the right thoracic cavity but does not reflect the severity of that injury. The highest concentration was found in the patient failing non-operative management. The presence of intrathoracic bile in selected patients who sustain RST penetrating trauma, with liver injury, does not preclude non-operative management. Our study suggests that monitoring chest tube effluent bilirubin may provide helpful information when managing a patient non-operatively.     

Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder

OBJECTIVE

To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)‐mediated neurogenic bladder in rats.

MATERIALS AND METHODS

In all, 40 female Sprague‐Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 µg/rat), VEGF (2 µg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (α‐actin), Masson’s trichrome and protein gene product 9.5, respectively.

RESULTS

Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups.

CONCLUSIONS

This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.     

Clinical value of a high-fat and low-carbohydrate diet before FDG-PET/CT for evaluation of patients with suspected cardiac sarcoidosis

Background

We hypothesized that a high-fat and low-carbohydrate (HFLC) diet before FDG-PET/CT could identify patients with active cardiac sarcoidosis (CS).

Methods

Fifty-eight sarcoidosis patients with a suspicion of CS consumed a HFLC diet before FDG-PET/CT. Clinical, electrical, and other imaging investigations were compared to PET results.

Results

Using Japanese Ministry of Health and Welfare (JMHW) criteria as a gold standard, 21% (12/58) of patients had a CS. Sensitivity and specificity of PET (visual analysis) were 83% (10/12) and 78% (36/46), respectively, with a very good interobserver agreement (k = 0.86). 70% (7/10) of the patients with a positive PET and negative JMHW criteria exhibited abnormalities suggestive of CS either on MR (n = 3) or SPECT (n = 4). Comparison with the presence of delayed enhancement on magnetic resonance imaging helped to classify patients with active (PET positive) or non-active CS (PET negative). In addition, when MR and PET were both negative, none of the patients met the JMHW criteria. PET response under treatment was concordant with clinical evolution in 11/13 patients.

Conclusions

FDG-PET/CT after HFLC diet is a sensitive tool for the diagnosis of active CS. Combined use of PET and MR is promising for the detection and characterization of CS lesions.     

Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.     

Celiac axis and superior mesenteric artery: danger zone for left nephrectomy

We report two cases of iatrogenic occlusion of the superior mesenteric artery (SMA) and celiac axis (CA) during left nephrectomy. A patient with a urothelial carcinoma (open surgery) and one with coralliform calculi (laparoscopy) experienced injury to both the SMA and/or CA due to bulky perihilar adenopathy and kidney adherence to surrounding tissue. The cancer patient survived after fast repair. Repair was delayed in the second patient who subsequently died. It is essential to identify each arterial branch carefully on the preoperative CT-scan to identify any duplicate renal arteries and avoid mistaking the SMA and/or CA for the renal artery.     

The hemodynamic behavior of arterial anastomosis using fibrin sealant: experimental study in swine

The wide use of biological sealants as a reinforcement for arterial sutures and the small experimental base in literature motivated this study. Our aim was to evaluate the flow, tear pressure, and the need of reinforcement stitches in sutured arteries after a cross-section. This research project complied with the Helsinki convention. The Tissucol (Baxter) fibrin sealant was used in all experiments. The femoral and carotid arteries of 17 swine from the same breed (weighing from 15 to 20 kg) were cross-sectioned after heparinization and subjected to anastomoses using a single continuous plane of 7-0 prolene. We worked with 68 artery samples, 34 in the treatment group and 34 in the control group. For each animal, one carotid and one femoral artery randomly received fibrin sealant with the contralateral side being used as a control. The need and the number of reinforcement stitches were recorded. Ten minutes after protamine infusion, the animals were sacrificed and the arteries were catheterized respecting 1 cm proximal and distal. The arteries were measured and placed on a flow meter to evaluate the flow rate of 10 mL of 0.9% NaCl in a 50 cm high column. The arteries were then subjected to air infusion at increasingly higher pressures (stepwise increases of 25 mm Hg), the grafts were dipped in 0.9% NaCl solution, the first air leakage was observed, and the tear pressure recorded. Data was analyzed with EpiInfo 6 data manager. The external diameters and thickness of the arteries were similar in both the treatment and control group. There was no significant difference between the groups regarding the tear pressure (P = 0.329), flow rate (P = 0.943), and the number of samples with a tear pressure above 200 mm Hg. However, the sealant reduced the number of reinforcement stitches necessary (P = 0.029). We conclude that fibrin sealant reduces the need of additional stitches; however, it does not change the tear pressure nor significantly reduces the flow.     

Long-term survival of autotransplanted major pelvic ganglion in the corpus cavernosum of adult rats

PURPOSE: Neurogenic impotence is a common complication after radical pelvic surgery, irradiation or perineal trauma. Neuronal transplantation is a new frontier for treating neurological disorders. We investigated whether the major pelvic ganglion can survive and become functional after being implanted into the corpus cavernosum in adult rats. MATERIALS AND METHODS: Adult male rats (13) were divided into 3 groups and sacrificed at 3 time points, namely 30 (4), 60 (5) and 90 (4) days. All rats underwent excision of the right major pelvic ganglion and left cavernous nerve. The right ganglion was implanted into the right crus of the penis. Electrostimulation was applied to the left major pelvic ganglion and cavernous nerve (1.5 mA.) and right crus (10 mA.) at sacrifice. The crural region and left ganglion were then excised for immunostaining of neuronal nitric oxide synthase (nNOS), protein gene product 9.5 and growth associated protein 43. Image analysis was used to calculate the area stained in pixels. Electron microscopy of the implanted area was performed to assess neuronal survival. RESULTS: Although the degree varied, all neuronal implants survived after transplantation. The response to electrostimulation was insufficient to produce erection. No difference was noted among the areas of nNOS staining when specimens from the 3 time points were compared. The area of expression of nNOS, protein gene product 9.5 and growth associated protein 43 was larger in the implanted area than in the surrounding cavernous tissue. Under electron microscopy most surviving implants showed normal ultrastructure, although areas of fibrotic replacement were seen in several implants. CONCLUSIONS: Our results show that the autotransplanted major pelvic ganglion expresses nNOS, protein gene product 9.5 and growth associated protein 43, and survived up to 90 days after implantation into the corpus cavernosum. Further studies with fetal neuronal tissue seem warranted.