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Biomedical subjects

C Combe

Publications and source records attributed to C Combe.

At least 37 records · Page 2Linked to original sources

MPO-ANCA-Positive crescentic glomerulonephritis: a distinct entity of scleroderma renal disease?

Scleroderma renal crisis is characterized by intimal thickening of the afferent glomerular arterioles resulting in hypertension and fibrinoid necrosis of the capillary tuff. We report a 67-year-old man with long-standing systemic sclerosis who developed normotensive progressive renal failure, proteinuria, and a nephritic urinary sediment with serum myeloperoxidase-antineutrophil cytoplasmatic antibodies (MPO-ANCA). Renal biopsy showed pauci-immune crescentic glomerulonephritis but none of the typical vascular changes of scleroderma renal crisis. Because comparable cases have recently been reported from Japan, normotensive MPO-ANCA-positive crescentic glomerulonephritis may form an entity of progressive renal failure in scleroderma.

Aged↗

Thymoma associated with myasthenia gravis and minimal lesion nephrotic syndrome.

A nephrotic syndrome has been observed rarely in association with thymoma. In most of the reported cases, it occurs when the thymoma is in remission; histological examination generally shows minimal change disease. We report a case of a 43-year-old man presenting with minimal lesion nephrotic syndrome at the time of the diagnosis of thymoma and myasthenia gravis, which persists despite remission of the thymoma. The role of a disorder of T-cell function and of circulating cytokines is discussed.

Adult↗

[Effect of inhaled nitric oxide in a patient with intracranial hypertension].

Inhaled nitric oxide (NO) may be beneficial in patients with acute respiratory distress syndrome (ARDS). The effects of inhaled NO on intracranial pressure have not yet been assessed. This case shows the beneficial effects of inhaled NO in a patient with ARDS and intracranial hypertension.

Administration, Inhalation↗

Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins.

BACKGROUND: Chronic interstitial scarring contributes to the progression of renal failure in glomerular disease but its cause is unknown. The development of proteinuria could stimulate tubular cells to release cytokines, chemoattractants and matrix proteins into the interstitium, thus contributing to interstitial disease. METHODS: Polarized human tubular epithelial cells were grown on permeable supports and exposed to serum proteins on their apical surface. The release of tumour necrosis factor alpha(TNFalpha), platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) by the cells was measured using immunoassays. RESULTS: Under control conditions there was polarized release of PDGF-AB with predominant basolateral secretion (basolateral to apical ratio 4.7+/-1.6). MCP-1 release was less polarized (ratio 1. 7+/-0.5). TNFalpha was not detected. Exposure of the cells to normal human serum proteins on their apical side increased basolateral release of PDGF-AB (1.7+/-0.4 fold) and MCP-1 (2.4+/-0.2 fold). Fractionation of the serum showed that this effect on human tubular epithelial cells was reproduced by a fraction of molecular weight 40-100 kDa. The predominant proteins in this fraction were albumin and transferrin but these purified proteins alone did not alter secretion of PDGF-AB or MCP-1. CONCLUSION: This data demonstrates that human tubular cells exposed to proteins, which would be filtered in glomerular disease, produce inflammatory mediators with the potential to stimulate inflammation and scarring in the interstitium of the kidney.

Blood Proteins↗

Bone mass and dynamic parathyroid function according to bone histology in nondialyzed uremic patients after long-term protein and phosphorus restriction.

One year of a very low protein diet (VLPD) can reverse secondary hyperparathyroidism in uremic patients. We studied bone histology, bone mineral density (BMD), and dynamic parathyroid function (calcium/PTH curves) in 16 nondialyzed patients with advanced renal failure who had been receiving a VLPD for a mean of 5 yr (mean protein intake, 0.34 +/- 0.12 mg/kg x day; mean phosphorus intake, 8.2 +/- 2.1 mg/kg x day) and daily supplementation with essential amino acids and their ketoanalogs (1000 IU vitamin D2 and 1-2 g calcium carbonate). Three patients exhibited a high bone formation rate (BFR), 7 patients had normal bone remodeling, and 6 patients had a low BFR, including 2 with osteomalacia and 4 with adynamic bone disease without aluminum overload. A longer diet duration and lower caloric intake were associated with low BFR. More than half of the patients exhibited moderate or severe osteoporosis at the appendicular skeleton. The t score of femur BMD explained 65% of the BFR variance. Patients with a low BFR had a dynamic parathyroid function similar to that of patients with a normal BFR, except they had a lower capacity to buffer a calcium load, whereas patients with a high BFR had a higher basal PTH/maximum PTH and a steeper calcium/PTH curve slope; the calcium set-point was identical in the three groups.

Adult↗

Volume flow measurement in hemodialysis shunts using time-domain correlation.

Volume flow was measured in 58 hemodialysis shunts (32 grafts and 26 radial fistulas) using the color velocity imaging-quantification method. This method is based on time-domain correlation for velocity calculation and integration of time-varying velocity profiles generated by M-mode sampling. Measurements were made in the brachial artery to estimate radial fistula flow or directly in the grafts. Intraoperator reproducibility was 14.9% for fistulas and 11.6% for grafts. Flow rate was significantly lower in abnormal shunts associated with a functional disorder or a morphologic complication (808 ml/min +/- 484) than in shunts associated with no abnormalities (1401 ml/min +/- 562). Receiver operating characteristic curves showed that a flow rate of 900 ml/min for fistulas and 1300 ml/min for grafts provided 81% and 79% sensitivity and 79% and 67% specificity, respectively. A functional disorder or a morphologic complication was associated with all fistulas and grafts in which flow rates were lower than 500 ml/min and 800 ml/min, respectively.

Adolescent↗

[Secondary cubital paralysis from prolonged thoracic drainage].

In intensive therapy patients, thoracic drains are usually inserted in the lateral part of thorax with the extension tube crossing the posterior aspect of the upper limb. We report the cases of two sedated patients who experienced ulnar palsy from a thoracic drain located behind their elbow.

Accidents, Traffic↗

[Effectiveness of valproic acid for postanoxic action myoclonus (Lance-Adams syndrome)].

We describe the case of a patient who experienced postanoxic action myoclonus after a transient cardiopulmonary arrest. Whereas benzodiazepines (clonazepam, midazolam, diazepam) were inefficient, valproic acid allowed a full control of the myoclonus. It is essential that the distinction between postanoxic action myoclonus and posthypoxic seizures is made early to avoid a delayed appropriate therapy and erroneous prognostic conclusions.

Adult↗

Worksite and family education for dietary change: the Treatwell 5-a-Day program.

The National Cancer Institute's '5-a-Day for Better Health Campaign is examining the efficacy of interventions in increasing the consumption of fruits and vegetables to five or more servings a day. This paper presents the study design, intervention and baseline survey results of the Treatwell 5-a-Day project, a randomized, controlled worksite-based intervention study. Twenty-two community health centers were randomly assigned to either a Minimal Intervention, Worksite Intervention or Worksite Plus Family Intervention. The Worksite Intervention included participation of employee advisory boards, programs aimed at individual behavior change and programs aimed at changes in the worksite environment. The Worksite Plus Family Intervention incorporated family-focused interventions into the worksite program, including a learn-at-home program, family newsletter, family festival and materials mailings. A self-administered survey was conducted prior to randomization (mean response rate: 87%, n = 1359). Twenty-three percent reported consuming five or more servings of fruits and vegetables a day. Consumption of fruits and vegetables was directly associated with level of household support for healthy eating. The Treatwell 5-a-Day intervention model has the potential to enhance existing worksite-based intervention through incorporation of its family focus, especially given the association of household support with individual eating habits.

Adult↗

[Spontaneous rupture of the esophagus (Boerhaave syndrome) in a patient with scleroderma treated by continuous ambulatory peritoneal dialysis].

Esophageal involvement is a common situation found in 50 to 80% of patients with scleroderma, but Boerhaave's syndrome is rare in this context. The authors report the first case of spontaneous esophageal rupture occurring in a chronic renal failure patient treated by continuous ambulatory peritoneal dialysis. In this observation, sclerodermal esophageal dyskinesia, chronic renal failure which is a classical cause of vomiting and the peritoneal dialysis which play an increasing role in the intraabdominal pressure are potential contributing factors to Boerhave's syndrome. In such patients presenting risk factors, even if they are asymptomatic, it seems reasonable to propose esophageal explorations with manometry or/and endoscopy looking for dyskinesia or other complications of gastro-esophageal reflux.

Esophageal Diseases↗

Henoch-Schönlein purpura with immunoglobulin A nephropathy and abnormalities of immunoglobulin A in a Wiskott-Aldrich syndrome carrier.

Abnormalities of immunoglobulin A1 (IgA1) glycosylation have been described in patients with IgA nephropathy (IgAN), whether primitive or secondary to Henoch-Schönlein purpura. The Wiskott-Aldrich syndrome, an X-linked recessive disorder, is associated with abnormalities of IgA. Renal involvement with mesangial IgA deposition identical to that found in IgAN has been reported during this affection. We report the case of a female carrier of the Wiskott-Aldrich syndrome presenting with Henoch-Schönlein purpura and abnormalities of IgA glycosylation, as previously reported in patients with IgAN. The galactosylation abnormalities of IgA could be linked to the patient's status as carrier of the Wiskott-Aldrich syndrome and could contribute to the pathogenesis of IgAN.

Adult↗

[Anuric renal insufficiency caused by bilateral ureteral lithiasis].

A 73-year-old man was admitted to the ICU for anuria. He reported no history of urinary disease. The abdominal roentgenography and two echographies showed an empty urinary bladder, a right ureteral calculus without dilatation of the urinary tract. Computed tomography demonstrated the presence of a left ureteral stone. Bilateral retrograde ureteroscopy and drainage allowed a rapid recovery. When the abdominal roentgenography and echography cannot explain the occurrence of anuria, the computed tomography, or better the helical CT, can demonstrate the presence of otherwise unrecognized calculi.

Acute Kidney Injury↗

Antioxidant effects of a supplemented very low protein diet in chronic renal failure.

Increased peroxidation of lipids in red blood cells (RBC) in patients with advanced chronic renal failure (CRF) reflects increased generation of reactive oxygen species (ROS), which may contribute to the metabolic damage induced by CRF and to its progression. We have evaluated parameters indicative of lipoperoxidation (LPO) of RBC at baseline in patients with CRF compared to controls, and the effects of a very low protein diet supplemented with amino and keto acids and vitamins A, C, E (VLPD) over a 6-month period. The presence of peroxidation damage in CRF patients before the administration VLPD was demonstrated by elevated levels of free malondialdehyde (MDA) (p < .0003) and decreased levels of polyunsaturated fatty acids (PUFA), particularly C20:4 (p < .001), C22:4 (p < .0001) and C22:5 (p < .0001) when compared to controls. Similarly, RBC vitamin E content was significantly decreased (p < .0001) while enzymatic activities were unalterated. VLPD reduced erythrocyte LPO as suggested by (a) decreased levels of free and total RBC MDA (p < .003 and p < .03, respectively), (b) increased levels of PUFA, particularly C22:4 and C22:5 (p < .003 and p < .03, respectively), and (c) increased levels of vitamins A and E (p < .001 and p < .04, respectively) as compared to prediet results. Antioxidant enzyme activities were not modified. These results suggest that VLPD has a protective role against LPO of erythrocytes in patients with CRF.

Adult↗

Low protein diet in uremia: effects on glucose metabolism and energy production rate.

Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we studied the effects of a LPD (0.3 g x kg(-1) x day(-1), supplemented with essential amino acids and ketoanalogs) in six patients suffering from chronic renal failure. After three months of diet, no significant change was observed concerning glomerular filtration rate, body wt, or arterial pH. In the postabsorptive state, plasma glucose and insulin levels were significantly lower, and energy production rose from 15.72 +/- 0.48 to 17.16 +/- 0.67 Cal x kg(-1) x min(-1) (P < 0.05). Insulin-stimulated glucose oxidation (2.36 +/- 0.29 vs. 3.37 +/- 0.35 mg x kg(-1) x min(-1); P < 0.05 at first clamp step) and nonoxidative disposal (P < 0.05 at both clamp steps) increased after LPD. This confirms that LPD ameliorates insulin sensitivity in CRF, even for low plasma insulin concentrations. Since energy production rate is increased by LPD, the caloric intake should be increased when protein intake is restricted.

Adult↗

Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular cells.

The adverse effects of acute renal ischemia are partly mediated through an infiltration of inflammatory cells into the tubulointerstitium. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by resident renal cells (endothelial cells and tubular cells) may facilitate this process. We investigated whether hypoxia stimulates the expression of ICAM-1 by cultured human proximal tubular cells (HPTC). Hypoxic culture conditions (PO2 < 4 kPa) stimulated the expression of ICAM-1 by HPTC in a time-dependent manner (P < 0.0001) as demonstrated by quantitative flow cytometry analysis. Quantitative PCR demonstrated an increase in ICAM-1 transcription. Re-oxygenation of tubular cells did not increase ICAM-1 expression further. TNF alpha concentration in culture supernatants increased with hypoxia, but blocking experiments demonstrated that TNF alpha was not implicated in hypoxia-induced expression of ICAM-1. Furthermore, the cytokines IL-6 and IL-1 beta were not involved, but the effect of hypoxia was blocked by PDTC, an antioxidant that may inhibit the activation of the transcription factor NF-kappa B. These data demonstrate that hypoxia is a stimulus that induces the synthesis and expression of the adhesion molecule ICAM-1, presumably via the activation of NF-kappa B.

Antioxidants↗

A low-protein diet improves insulin sensitivity of endogenous glucose production in predialytic uremic patients.

A low-protein, low-phosphorus diet (LPD) has been shown to improve insulin sensitivity in uremic patients; however, this improvement has not been studied at low physiologic concentrations of plasma insulin, and the metabolic pathways concerned with this improvement have not been located. We used the glucose clamp technique at a low (0.25 mU.kg-1.min-1) level of hyperinsulinemia associated with the infusion of D[6,6-2H2] glucose to assess the insulin sensitivity of endogenous glucose production (EGP). Eight nondialyzed uremic patients were studied before and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg, and 146 kJ/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma glucose and insulin declined after 3 mo of the diet (plasma glucose: 5.0 +/- 0.1 mmol/L before compared with 4.7 +/- 0.1 mmol/L after the LPD, P < 0.05; plasma insulin: 82.4 +/- 20.7 pmol/L before compared with 48.8 +/- 6.0 pmol/L after, P < 0.05). Postabsorptive glucose turnover rates did not change with the diet (2.06 +/- 0.14 mg.kg-1.min-1 before compared with 2.11 +/- 0.17 mg.kg-1.min-1 after LPD; NS). The insulin metabolic clearance rate was enhanced after the diet, so a lower level of hyperinsulinemia was obtained during the clamp (168.8 +/- 28.1 pmol/L before compared with 115.2 +/- 14.7 pmol/L after; P < 0.05). However, EGP was more easily inhibited after the diet (0.90 +/- 0.31 mg.kg-1.min-1 before compared with 0.30 +/- 0.17 mg.kg-1.min-1 after; P < 0.05), providing evidence of an improved insulin sensitivity of this parameter. This beneficial influence takes place at a physiologic level of hyperinsulinemia, and it probably plays an important role in the better glucose tolerance that has been reported in uremic patients on an LPD. An abnormal insulin sensitivity of EGP may participate in the disturbances of glucose metabolism in chronic renal failure.

Adult↗

Cyclosporin-A- and angiotensin-II-induced vasoreactivity in isolated glomeruli and cultured mesangial cells, 4 and 24 h after renal mass reduction: role of vasodilatory prostaglandins.

Subtotal nephrectomy in the rat is followed by early hypertrophy and functional adaptation of the remnant glomeruli in which mesangial cells seem to play a leading part. Using a morphoquantitative approach, we assessed the vasoconstrictive response to 1 microM cyclosporin A (CsA) or 0.1 microM angiotensin II (AII) of isolated glomeruli and cultured mesangial cells obtained from normal rats and from rats after five-sixths nephrectomy. In normal rats, a significant reduction of glomerular size was observed after the administration of vasoactive agents (-14% after 30 min exposure to CsA or AII). After five-sixths nephrectomy the vasoconstrictive response, which was preserved at the 4th hour (-12% at the 30th minute), disappeared at the 24th hour (-1.5% at the 30th minute), but was maintained in animals pretreated with indomethacin (-10% at the 30th minute). Similar responses were observed with cultured mesangial cells at the first passage. Inhibition of prostaglandin synthesis abolishes the adaptative adjustments observed in partially nephrectomized rats during the first days after surgery. These findings suggest that renal vasodilatory prostaglandins may participate in the compensatory hemodynamic adjustments following subtotal nephrectomy.

Adaptation, Physiological↗