Short‐term intravenous insulin infusion is associated with reduced expression of NADPH oxidase p47phox subunit in monocytes from type 2 diabetes patients

Hyperglycemia is a well‐known inducing factor of oxidative stress through activation of NADPH oxidase. In addition to its plasma glucose lowering effect, insulin may also have antioxidant activity and was shown to downregulate NADPH oxidase expression in vitro. In this study, we show that a short‐term (3‐day) intravenous insulin infusion in patients with type 2 diabetes induces normalization of both glycemia and mRNA expression of circulating monocyte p47^phox subunit.     

Results of surgery for irreversible moderate to severe mitral valve regurgitation secondary to myocardial infarction.

OBJECTIVE: Moderate to severe irreversible mitral regurgitation secondary to myocardial infarction is an independent risk factor for reduced long-term survival. Late effects of correction of mitral incompetence concomitant with coronary artery bypass grafting (CABG) are less well known and the choice of mitral valve procedure is still debated. METHODS: From 1988 to 1998, 93 consecutive patients (mean age 63+/-9 years) were treated for moderate to severe irreversible mitral regurgitation secondary to myocardial infarction; 84 were in NYHA functional class III-IV and 19 were in cardiogenic shock. Thirty-seven patients underwent emergency surgery. Perioperative intraaortic balloon pump (IABP) was necessary in 33 patients. Follow-up ranged from 6 months to 12 years (mean 51 months+/-41). RESULTS: Mitral valve was repaired in 30 patients and replaced in 63. Replacement was preferably performed in patients with major displacement of papillary muscle and in patients with acute papillary muscle rupture. CABG (3.4 distal anastomoses) was performed in all patients and was complete in 92%. Early mortality was 15% (14/93). Multivariable analysis identified need for IABP (P=0.005) and COPD (P=0.02) as risk factors for early death. Emergency surgery had only a trend (P=0.15) for increased mortality; age, low ejection fraction, repair vs. replacement had no influence. Actuarial survival rates at 1, 5 and 10 years were 81, 65 and 56%, respectively. Late survival was similar in patients with replacement or repair (P=0.46). At last follow-up, all but one patient were in NYHA functional class I or II. CONCLUSIONS: Combined mitral valve procedure and myocardial revascularization, as complete as possible, for moderate to severe mitral regurgitation secondary to myocardial infarction achieve satisfactory early and late outcome despite the increased operative mortality. Acute papillary muscle rupture, severe restriction of the mitral valve by major displacement of the papillary muscle are better managed by valve replacement.     

Complications of plate fixation in metacarpal fractures

BACKGROUND: The objective of this study is to assess the complications after open reduction and plate fixation of extra-articular metacarpal fractures. METHODS: We retrospectively reviewed the clinical and radiologic records of 129 consecutive patients with 157 metacarpal fractures treated by open reduction and internal fixation with plates between 1993 and 1999. Intra-articular fractures and fractures of the thumb metacarpal were excluded. Eighty-one patients (64 men and 17 women) with 104 fractures were available for review, at an average follow-up of 13.6 months (range, 6-27 months). RESULTS: Twenty-eight patients (35%) and 33 fractures (32%) had one or more complications, including difficulty with fracture healing (12 patients [15%]), stiffness (eight patients [10%]), plate loosening or breakage (seven patients [8%]), complex regional pain syndrome (two patients), and one patient who developed a deep infection. CONCLUSION: Despite technical advances in implant material, design, and instrumentation, plate fixation of metacarpal fractures remains fraught with complications and unsatisfactory results.     

Long-term kidney graft survival across a positive historic but negative current sensitized cross-match

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.     

Understanding risk assessment in cardiac surgery patients

Understanding the risk of surgery in valvular disease is of interest because aging of the population renders decision making more difficult and the magnitude of risk will influence not only the decision to intervene but also the choice of intervention and its timing. To assist clinicians in assessing the risk of cardiac surgery, multivariate risk scores are increasingly used to estimate operative mortality. Overall, the currently available scores, mostly U.S. Society of Thoracic Surgeons score and European System for Cardiac operative Risk Evaluation, achieve acceptable discrimination but suboptimal calibration in estimating the operative mortality of heart valve surgery. The intrinsic limitations of scoring systems highlight the fact that risk scores should be integrated into clinical judgment but should not be a substitute for it. A multidisciplinary approach involving cardiologists, cardiac surgeons, and anesthesiologists is required for this purpose, especially in high-risk patients.     

'MRI-tis' in the early diagnosis of axial SpA: issues and limitations

Sacroiliitis on conventional radiography, a key diagnostic feature of axial spondyloarthritis (SpA), often appears only late in the disease course. With the introduction of potent biologic agents that may also be effective in early disease, diagnostic techniques that can identify SpA early in the disease course would be highly beneficial to patients. MRI has been proposed as a novel diagnostic tool for early axial SpA based on the visualization of active inflammatory lesions in established axial SpA, as well as in pre-radiographic axial SpA. Accordingly, MRI is already widely used in clinical practice and has been included in new classification criteria. However, the specificity and predictive value of MRI lesions for the development of axial SpA remain to be fully defined and validated. Most data come from cross-sectional analyses and have not been validated in prospective studies, and the few available prospective studies were performed in highly selected patient populations and have assessed the value of MRI for the prediction of sacroiliitis rather than axial SpA. Also, some studies have indicated considerable diversity in the pattern and extent of MRI lesions, and suggest that many lesions are not specific for SpA. Prospective, longitudinal studies are needed to validate the utility of this new imaging modality for the diagnosis of axial SpA.     

Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

Background Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C. Methods A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m²) combined with irinotecan (360 mg/m²) in 2 L/m² of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m²) and leucovorin (20 mg/m²) intravenously, resulting in tritherapy. Results Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). Conclusions This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.     

Prognosis and histopathologic features in papillary tumors of the pineal region: a retrospective multicenter study of 31 cases

Papillary tumor of the pineal region (PTPR) is a recently described tumor entity thought to arise from the specialized ependyma of the subcommissural organ. Whereas histologic features of PTPR are well defined, data on the prognostic value of PTPR remain scarce. We therefore investigated clinicopathologic features, including data on progression-free survival and overall survival, in a retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged from 5 to 66 years (median age, 29 years). Histologically, all tumors were characterized by an epithelial-like growth pattern in which the vessels were covered by layers of columnar or cuboidal tumor cells forming perivascular pseudorosettes. Most of the tumor cells showed strong expression of neuron-specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin. Most PTPRs examined also expressed microtubule-associated protein-2. Expression of synaptophysin, epithelial membrane antigen, transthyretin, neural cell adhesion molecule, and nestin was encountered in some tumors. Gross total resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy on resection of the primary tumor. Nevertheless, the majority of patients experienced recurrences; 5-year estimates for overall survival and progression-free survival were 73% and 27%, respectively. To conclude, the clinical course of PTPR is characterized by frequent local recurrence, and the value of radiotherapy on disease progression will need to be investigated in future prospective trials.     

Glutamate receptor changes associated with transient anoxia/hypoglycaemia in hippocampal slice cultures

Transient anoxia/hypoglycaemia in organotypic hippocampal slice cultures, a model of transient brain ischaemia, ultimately results in delayed cell death. Although the mechanisms underlying this delayed death remain unknown, an increase in excitatory drive has been postulated. We report here that transient anoxia/hypoglycaemia in rat hippocampal slice cultures resulted in a 70-80% enhancement of evoked, alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor-mediated, excitatory responses lasting over 60 min. This effect was prevented by blockade of N-methyl-d-aspartate (NMDA) receptors, did not involve changes of paired-pulse facilitation ratio, but was associated with a 50% increase in amplitude, but not frequency, of spontaneous miniature excitatory postsynaptic currents (mEPSCs). Consistent with this, paired recordings revealed the appearance of AMPA receptor-mediated EPSCs at previously silent synapses and occlusion by prior induction of long-term potentiation (LTP). Transient anoxia/hypoglycaemia further resulted in a 63% potentiation of evoked NMDA receptor-dependent synaptic responses, accounting for the 20% increase in ratio of AMPA to NMDA responses. No change in rectification properties of AMPA receptor-mediated currents could be detected within the first hour following anoxia/hypoglycaemia-induced potentiation. Western blot analyses of slice cultures exposed to either control conditions or a short anoxia/hypoglycaemia revealed a marked, 50-70% increase of GluR1, GluR2/3 and NR1 subunits 1 h, but not 15 min, after the anoxic/hypoglycaemic episode. This increase was blocked by an inhibitor of protein synthesis. Together these results indicate that a transient anoxia/hypoglycaemia is associated with a marked enhancement of excitatory transmission sharing similarities with the mechanisms underlying LTP, and is correlated with an increased synthesis of excitatory receptor subunits.