Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes.

In patients with Type 2 diabetes, the appropriate intensity of glucose control is determined by age, life expectancy, and the presence of concomitant disease. Geriatric patients are especially susceptible to hypoglycaemia and therefore particular care should be taken in this group characterized by polypharmacy, renal or hepatic dysfunction, cardiovascular multimorbidity and malnutrition. As hypoglycaemia is a significant cause of morbidity and mortality, treatment regimens for diabetes should minimize the occurrence of hypoglycaemic episodes and be tailored to the patient's individual needs. The pharmacological options for treating Type 2 diabetes have increased considerably and the risk of hypoglycaemia of the currently available drugs varies considerably. Metformin, thiazolidinediones, and acarbose, oral antidiabetic drugs that decrease insulin resistance or postprandial glucose absorption, are associated with a low risk of hypoglycaemia. These drugs can also be used effectively in various combination regimens; however, by improving insulin sensitivity, combinations of metformin and thiolidinediones with sulphonylureas or meglitinides may considerably increase the risk of hypoglycaemia. On account of its complex pharmacoprofile glibenclamide is a problematic substance carrying a high risk of hypoglycaemia. There are limited preliminary data indicating that, under routine conditions, glimepiride may be associated with a lower risk of hypoglycaemia than glibenclamide and is no more likely to cause hypoglycaemia than other shorter-acting agents such as gliclazide and glipizide. Nateglinide and repaglinide as short-acting insulin secretagogues may be associated with a reduced risk of hypoglycaemia compared with glibenclamide, in particular when dosed flexibly. Repaglinide might be beneficial in individuals with renal impairment.     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Spinal fluid dynamics during thoracic- and thoracoabdominal aortic surgery.

AIM: The intention was to investigate cerebrospinal fluid pressure (CSFP) and volume of cerebrospinal fluid (CSF) drained during and after thoracic- and thoracoabdominal aneurysm repair. The findings were related to the occurrence of postoperative neurologic deficits. METHODS: Twenty-nine patients (12 with thoracic and 17 with thoracoabdominal aortic aneurysm) were operated without shunting or extracorporeal circulation. For monitoring of CSFP an intrathecal catheter was placed in all patients. The volume of CSF withdrawn intraoperatively, on the day of operation as well as on the 1st and 2nd postoperative day was recorded. RESULTS: Twenty-six patients had no postoperative neurologic sequelae. One patient had postoperative paraplegia while 2 had paraparesis. The three patients with neurologic sequelae had higher CSFP intraoperatively than those without neurologic symptoms (P=0.04). Median CSFP during aortic cross-clamping was 19 mmHg and 10 mmHg and the median volumes of CSF drained on the day of operation 210 and 85 mL in the two groups, respectively. There was a significant positive correlation between CSFP and central venous pressure. CONCLUSIONS: A higher intraoperative CSFP was observed in patients with neurologic sequelae following thoracic- and thoracoabdominal aneurysm repair. Further, there was a tendency of higher volumes of CSF drained in this group of patients. Although, the series is too small to allow firm conclusions, it supports the view that CSFP monitoring and drainage is beneficial during thoracic- and thoracoabdominal aneurysm repair.     

Horizontal advancement flap for lateral dorsal nasal defects

BACKGROUND: Repairing dorsal nasal defects is a frequent challenge for dermatologic surgeons, mainly due to the high frequency of basal cell carcinomas on this site. Obvious scars, mismatched skin and distortion of the nasal contour are the surgical hazards that must be avoided in these cases. AIM: Our aim was to perform surgery involving a simple flap in order to repair medium to large defects on the dorsal side of the nose. METHODS: The dorsal horizontal advancement flap was studied in 12 patients, in order to evaluate the benefits and limits of this surgical procedure. RESULTS: The resulting scars on most of our patients were well-camouflaged among their natural skin lines, and there was neither distortion of the alar contour nor the nostril. CONCLUSIONS: This flap is easy to perform and, in selected cases, provides an outstanding alternative to second-intention healing, full-thickness skin grafts, transposition, rotation and pedicle flaps.     

Ketorolac during the induction phase of cyclosporin-A therapy.

PURPOSE: The aim of this study was to determine if the concomitant use of ketorolac 0.4% and cyclosporin-A improves patient comfort during the induction phase in treating chronic dry eye disease. METHODS: Patients (n = 52) with clinically diagnosed dry eye were randomized to receive either cyclosporin-A monotherapy twice-daily (BID) or a BID adjunctive regimen of ketorolac, followed by the instillation of cyclosporin-A 10 min later. Study visits were at baseline, week 2, and week 6. At each study visit, patients underwent an evaluation for corneal staining, Schirmer's scores, and tear break-up time tests. Patients were asked to rate ocular comfort on a 4-point scale and to complete the ocular surface disease index (OSDI). Changes from baseline readings were recorded at week-2 and week-6 visits, and final patient success on treatment regimen was evaluated at week 6. RESULTS: After 6 weeks, the mean ocular comfort score of adjunctive patients improved 2.55 +/- 0.95 points, versus 1.53 +/- 0.91 points for monotherapy (P = 0.309). The adjunctive regimen provided significantly greater corneal staining reductions versus monotherapy, mean reduction in staining of 1.74 +/- 0.9, versus 1.27 +/- 0.56 (P = 0.044). CONCLUSIONS: Concurrent ketorolac 0.4% use with cyclosporin-A significantly reduced corneal staining and increased comfort in the induction phase.