Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes.

AIMS: Interindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FRGLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR). METHODS: FRGLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FRGLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90-60 (G2); 59-30 (G3); and<30-16 (G4) mL/min/1.73 m2. Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6mmol/L); intermediate (6-11mmol/L); and high (>11mmol/L). RESULTS: Median (interquartile range, IQR) FRGLU levels were blood glucose-dependent: 99.90% (0.05) for low (n=106); 99.90% (0.41) for intermediate (n=288); and 96.36% (12.57) for high (n=243) blood glucose categories (P<0.0001). Also, FRGLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n=135); microalbuminuria, 96.56% (5.94) (n=77); macroalbuminuria, 99.12% (5.44) (n=31; P<0.001); eGFR G1, 94.13% (16.24) (n=111); G2, 96.35% (11.94) (n=72); G3 98.88% (7.59) (n=46); and G4, 99.11% (2.20) (n=14; P<0.01). On multiple regression analyses, FRGLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group. CONCLUSION: High glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels>11mmol/L.

Type III open tibia fractures in low-resources setting. Part 3: achievement of bone union and treatment of segmental bone defects.

After presentations of the principles of limb salvage and soft-tissue coverage for Gustilo III open tibia fractures, this third part is dedicated to management of tibial non-unions in low-resource settings. Inter-tibiofibular grafting and the induced membrane technique are preferred because they make it possible to deal with almost all situations. Key technical points of these methods are presented, followed by treatment guidelines based on Catagni's classification and bone defect size.

Type III open tibia fractures in low-resource setting. Part 2: soft-tissue coverage with simple, reliable and replicable pedicle flaps.

After limb salvage based on debridement and external fixation, Gustilo IIIB open tibia fractures must undergo soft-tissue repair within 7 days. In low-resource setting, the coverage is performed with pedicled flaps only, which can be used by any orthopedic surgeon after minimal training. The authors describe here the simplified use of 7 basic flap transfers that can deal with almost all soft tissue defects. The diffusion of these techniques in developing countries is crucial for limiting functional and trophic effects related to prolonged exposure of the fracture site.

Type III open tibia fractures in low-resources setting. Part 1: strategy and principles of limb salvage.

In developing countries, road traffic accidents result in many cases of open trauma, especially fractures, with the tibia area at particular risk in motorcycle crashes. Despite a high prevalence of severe leg trauma with multi-tissue injuries, few studies have focused on the challenge of their reconstruction in these limited-resource settings. The first part of this review presents the surgical strategy. Limitations and principles of initial limb salvage are detailed. Orthopedic procedures for early damage control, based on debridement and temporary bone stabilization, are often required. The priority is to shorten the time to initial surgical management to avoid infection, which jeopardizes reconstruction.

Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man.

Study of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.

Use and utility of ankle brachial index in patients with diabetes.

Ankle brachial index (ABI) is a simple method to screen peripheral arterial disease (PAD) and to evaluate cardiovascular (CV) prognosis in the general population. Measuring it requires a hand-held Doppler probe but it can be done also with an automatic device. ABI is an effective tool for clinical practice or clinical studies. However, in diabetic patients, it has some specific caveats. Sensitivity of the standard threshold of 0.9 appears to be lower in diabetic patients with complications. Moreover, highly frequent arterial medial calcifications in diabetes increase ABI. It has been demonstrated that measurements >1.3 are well correlated with both an increased prevalence of PAD and CV risk. Therefore, ABI thresholds of less than 0.9 and more than 1.3 are highly suspicious for PAD and high CV risk in diabetic patients. However, when there is concomitant clinical peripheral neuropathy or high risk of arterial calcification, the efficiency of ABI seems to be limited. In this case, other methods should be applied, toe pressure, in particular. Thus, the ABI could be used in patients with diabetes, but values should be interpreted with precision, according to the clinical situation.

[Delayed and fortuitous diagnosis of right diaphragmatic rupture during preoperative evaluation]. / Rupture diaphragmatique droite, de découverte tardive et fortuite à la consultation d'anesthésie.

Although diaphragmatic rupture occurs after violent blunt trauma, its diagnosis is often delayed. The intra-thoracic displacement of abdominal organs through diaphragmatic rupture may lead to early or delayed complications because of compression of heart and lungs or strangulation of the abdominal viscera. A 49-year-old woman was scheduled to undergo elective lumbar disc surgery in prone position. The preoperative chest radiograph revealed an abnormally elevated right hemi diaphragm with loops of colon filling the right costophrenic angle. The CT-scan confirmed right chronic diaphragmatic rupture with colon and liver herniations. Fifteen months previously, this woman had been involved in a traffic accident, with blunt right trauma resulting in right pelvic fractures. Perianaesthetic course increase the pre-existing mechanical risk of complications of chronic diaphragmatic rupture. Primary repair of right chronic diaphragmatic rupture through thoracotomy must be recommended. When another surgery must be done in emergency, the feasibility of regional anaesthesia should be considered.

N-acetyl-L-cysteine exhibits antitumoral activity by increasing tumor necrosis factor alpha-dependent T-cell cytotoxicity.

Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine (NAC) has been proposed for cancer treatment. Here we present a mechanism of action for NAC in cancer. Our data show that NAC (1) induces an early and sustained increase of membrane tumor necrosis factor alpha (TNF alpha) expression on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF-RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These effects result from an early inhibition of both TNF alpha and TNF-R shedding, as well as a later increase of the respective mRNA expression. Consequently, NAC confers cytotoxic properties to human PB T cells through a membrane TNF alpha-dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells. Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a membrane TNF alpha-dependent manner. Furthermore these mice were resistant to a second inoculation of L1210 cells without further treatment with NAC. Thus, NAC exhibits a potent antitumoral activity by modulating TNF alpha and TNF-R processing without showing any in vitro and in vivo toxicity.

[Treatment of subcutaneous ruptures of the Achilles tendon by percutaneous tenorraphy]. / Traitement des ruptures sous-cutanées du tendon d'Achille par ténorraphie percutanée.

Since 1982, the authors have progressively settled a technique to repair the calcaneal tendon, the result of which is a percutaneous tenorraphy exclusively used for more than 2 years. Their study includes 28 cases between 1989 and 1992, with an average post operative time of 15.6 months. The technique is fully described, its aim was to restore a normal length of the ruptured tendon in placing together the 2 tendinous ends during the required time to obtain natural regeneration of the Achilles tendon. It reduces the theoric immobilization time, makes rehabilitation easier as well as the return to sportive and professional activities. The suture was percutaneously made with a special material: A Dacron yarn with a 5 mm wide hook set on a 12 long flexible needle. The results were globally good and only very few complications were observed.