Ropivacaine preperitoneal wound infusion for pain relief and prevention of incisional hyperalgesia after laparoscopic colorectal surgery: a randomized, triple-arm, double-blind controlled evaluation vs intravenous lidocaine infusion, the CATCH study.

AIM: The abdominal incision for specimen extraction could trigger postoperative pain after laparoscopic colorectal resections (LCRs). Continuous wound infusion (CWI) of ropivacaine may be a valuable option for postoperative analgesia. This study was undertaken to evaluate the potential benefits of ropivacaine CWI on pain relief, metabolic stress reaction, prevention of wound hyperalgesia and residual incisional pain after LCR. A subgroup with intravenous lidocaine infusion (IVL) was added to discriminate between the peripheral and systemic effects of local anaesthetic infusions. METHOD: Patients were randomly allocated to three subgroups: CWI (0.2% ropivacaine 10 ml/h for 48 h); IVL (lidocaine 1.5% at 4 ml/h for 48 h); control group. RESULTS: In all, 95 patients were randomized (86 patients analysed). Postoperative pain intensity did not differ significantly between groups. Within the first 24 h after surgery, morphine requirement was significantly lower in the CWI group compared with the IVL group, but there was no significant difference compared with the control group (P = 0.02 and P = 0.15, respectively). The area of hyperalgesia did not differ significantly between subgroups, nor did the hyperalgesia ratio which was 1.2 cm (0.0-6.7) vs 1.9 cm (0.4-4.0) vs 2.0 cm (0.5-7.0) in the CWI, IVL and control groups respectively (P = 0.35). The number of patients reporting residual incisional pain after 3 months (3/26 vs 4/23 vs 4/23 in the CWI, IVL and control groups respectively) did not differ significantly between the groups, nor did their metabolic stress reactions. CONCLUSION: Ropivacaine CWI at the site of the abdominal incision did not provide any significant benefit either on analgesia or on the prevention of wound hyperalgesia after LCR.

Effect of protein binding on testosterone extraction by human cirrhotic liver: evidence for a dissociation-limited uptake.

Testosterone (T) is a protein-bound substance, the hepatic extraction of which largely exceeds the free plasma fraction. In this study we attempted to determine if the dissociation of T from plasma proteins is the limiting factor for testosterone hepatic uptake in patients with cirrhosis. For this purpose we measured the hepatic uptake of T and the peripheral plasma concentrations of the different fractions of the hormone (total, free, albumin-bound, and sex hormone-binding globulin (SHBG)-bound) in 12 men with alcoholic cirrhosis. The hepatic extraction of T (mean = 42%) greatly exceeded the non-SHBG-bound fraction of T (free T plus albumin-bound T: mean = 13%). Thus, a substantial amount of SHBG-bound T must have entered the liver. A theoretical extraction ratio was calculated based upon the dissociation rate constants of T from albumin and SHBG and upon an estimate of sinusoidal transit time of plasma through the liver. The similarity between the measured and expected values indicates that the limiting step in hepatic uptake of T might be SHBG binding.

Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts.

Serum sex hormone-binding globulin (SHBG), testosterone, non-SHBG-bound testosterone, androstenedione, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and cortisol were measured in 58 homosexual men seropositive for human immunodeficiency virus (HIV), all clinically asymptomatic (Centers for Disease Control 1993 classification stage A). The HIV patients were divided into four groups according to the CD4 lymphocyte count--group 1 (more than 500/microliters, N = 14), group 2 (between 350 and 500/microliters, N = 16), group 3 (between 200 and 349/microliters, N = 22) and group 4 (less than 200/microliters, N = 6)--and compared with 11 antibody-negative men as controls. The SHBG levels were significantly increased in groups 1, 2, 3 (p < 0.01) and 4 (p < 0.05) compared with controls, with no differences between groups of patients. Compared with controls, testosterone concentrations were significantly lower in group 4 (p < 0.05) and non-SHBG-bound testosterone levels were significantly lower in groups 1 (p < 0.05), 2 (p < 0.01), 3 (p < 0.001) and group 4 (p < 0.001); DHT and androstenedione levels were significantly lower in group 4 (p < 0.05) and DHEA levels were significantly lower in group 2, group 3 (p < 0.01) and group 4 (p < 0.05) than in controls. Cortisol levels were significantly increased in groups 1 and 4 (p < 0.05) and FSH and LH concentrations were not significantly higher in HIV-infected men than in controls. Also, the DHEA, androstenedione, non-SHBG-bound testosterone and DHT levels were correlated with CD4 cell counts, showing that hypogonadism occurs as the CD4 lymphocytes decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhabdomyolysis and acute renal failure in a patient with thermal injury.

We report a case of rhabdomyolysis with acute renal failure during recovery from thermal burn injury. The late occurrence of this unusual complication is emphasized and possible etiological factors are discussed.

Design of poly-epsilon-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery.

This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.

Seminal androgen concentrations and residual sperm cytoplasm.

To explore a possible link between seminal androgen concentrations and residual sperm cytoplasm, which constitutes one of the cytological anomalies of the spermatozoon middle piece, testosterone (T), delta4-androstenedione, the precursor of T during testicular androgen biosynthesis and the active metabolite of T, dihydrotestosterone, were assayed in the seminal fluid of 37 patients. A statistically significant correlation was found by linear regression (r = +0.380, P = 0.020, y = 0.02x + 0.45) between seminal T concentrations and the percentage of spermatozoa with a residual cytoplasmic droplet. Given the impact on fertility of residual sperm cytoplasm, assessment of seminal T concentrations could provide useful information on the fertility status of patients.

Hyaluronidase activity in serum of patients with monoclonal gammapathy.

Hyaluronidase and hyaluronic acid, two substances thought to be strongly implicated in carcinogenesis, were assessed in the plasma of 35 patients with newly documented monoclonal gammapathy and in 25 control patients. A significant increase was found in plasma hyaluronidase activity in the patients with monoclonal gammapathy. A statistically significant positive correlation was found between hyaluronidase activity and monoclonal immunoglobulin levels in plasma. An increase in serum hyaluronidase activities may be a response to the deleterious effect of hyaluronic acid in cell migration and tumor progression. Further studies are needed to assess the value of hyaluronidase activity as a marker of tumor progression.

Hyaluronan in horses: physiological production rate, plasma and synovial fluid concentrations in control conditions and following sodium hyaluronate administration.

REASONS FOR PERFORMING STUDY: Hyaluronic acid (HA) is an endogenous glycosaminoglycan used in the treatment of joint diseases, but medication control is required by horseracing authorities. Therefore, a medication control policy needs to be established. OBJECTIVES: To establish physiological plasma HA concentrations in post race horses, determine the HA endogenous production rate and document the disposition of HA after i.v. and intra-articular hyaluronic acid administration at recommended therapeutic doses. METHODS: Hyaluronan concentrations in plasma were determined using an ELISA specific test; concentrations in synovial fluid were determined using a radiometric binding assay. RESULTS: The overall mean plasma HA concentration in 120 post competition horses was 89 ng/ml. In a group of 6 experimental horses, synovial fluid control concentration was 328+/-112 microg/ml. After i.v. sodium hyaluronate administration (37.8 mg in toto), the terminal half-life was very short (43+/-29 mins) and after a delay of 3 h, the plasma concentration returned to control values. The endogenous HA production rate was 33-164 mg in toto per day, i.e. 1-4 times the recommended i.v. daily dose. Twenty-four hours after intra-articular administration, HA concentration was not significantly different from control values (328+/-112 microg/ml). CONCLUSIONS AND POTENTIAL RELEVANCE: Due to the rapid disappearance of HA from plasma after i.v. administration and from the joint after intra-articular administration, long-term detection needs a more appropriate approach to be developed.

[Chronic viral hepatitis C. Anatomoclinical and biological correlations]. / Hépatite chronique virale C. Corrélations anatomo-cliniques et biologiques.

OBJECTIVES: The relations between the severity of histopathological lesions and epidemiological, clinical and biological data were studied in 86 patients with chronic viral hepatitis C. PATIENTS AND METHODS: None of the patients had any clinical signs of decompensated liver disease. Three groups of patients were individualized according to histopathological findings: 17 (20%) had chronic persistent hepatitis, 48 (56%) had chronic active hepatitis without cirrhosis, and 21 (24%) had cirrhosis. RESULTS: Patients with cirrhosis differed significantly from patients in the two other groups for all biological parameters. With multivariate analysis, alkaline phosphatase activity and serum hyaluronic acid were two independent parameters significantly associated with cirrhosis. A serum hyaluronic acid level above 150 micrograms/L or alkaline phosphatase activity above normal were predictive of cirrhosis with a sensitivity of 87% and a specificity of 93%. None of the parameters in this study provided a clear distinction between patients with chronic persistent and chronic active hepatitis. CONCLUSION: Determination of serum hyaluronic acid and alkaline phosphatase activity as a non invasive index of cirrhosis could be useful for diagnosis and follow-up in patients with chronic viral hepatitis C.

[Recent aspects of liver biochemistry: from physiopathology to functional liver exploration]. / Aspects récents de la biochimie hépatique: de la physiopathologie á l'exploration functionnelle du foie.

The advent of liver transplantation and the availability of effective medical therapeutics have recently made possible treatments of chronic liver diseases. These improvements have evidenced new needs for evaluation of the treated patients. In this review, authors present new biochemical liver tests proposed for a better monitoring in the course of the disease, to assess the therapeutic response in clinical trials and to reduce the number of liver biopsies. The different aspects of this paper concern the evaluation of hepatic uptake and biliary elimination, cholestasis, jaundice, cellular injury, fibrosis and liver tumor.

[Radioimmunoassay of salivary l7 alpha-hydroxyprogesterone. Values obtained in healthy subjects and in patients treated for congenital hyperplasia of the adrenal glands]. / Radioimmunodosage de la 17 alpha-hydroxyprogestérone salivaire. Valeurs obtenues chez les sujets sains et chez les patients traités pour hyperplasie congénitale des surrénales.

The authors describe a method for the radioimmunoassay of 17 alpha-hydroxyprogesterone in the saliva. The limit of detection is 1.96 fmole/tube. Salivary 17 alpha-hydroxyprogesterone was measured in control subjects. Values found were of 296 +/- 115 pmol/l in the male, and 251 +/- 23 pmol/l in the female during the follicular phase and 401 +/- 94 pmol/l during the luteal phase, and 115 +/- 30 pmol/l in the prepubertal child. Concentrations were much higher in the newborn and decreased during the first days of life. Variations in salivary concentrations were compared with those in plasma 17 alpha-hydroxyprogesterone during the 24-hour period and with the Synacthene stimulation test. The excellent correlation (r = 0.0969) between salivary 17 alpha-hydroxyprogesterone and plasma 17 alpha-hydroxyprogesterone in 28 patients being treated for 21 hydroxylase deficiency makes it possible to suggest salivary assay in place of plasma assay in the therapeutic follow-up of such patients.

[Enzyme calibrators: principle and practical use]. / Le calibrage en enzymologie clinique: principe, conditions d'application et résultats.

Results of catalytic activities of enzymes are highly dependent on the measurement procedures and on local conditions. Thus, only poorly marked improvement of interlaboratory comparability of results have been observed in clinical enzymology. To solve this problem, SFBC and IFCC have proposed to use "validated enzyme calibrators". Standardised operating procedures adapted to 37 C have been developed by IFCC for the most commonly used enzymes in clinical chemistry, and will be soon published. Reference materials which have been certified with these SOPs can be used as calibrators for a set of measurement methods which exhibit the same analytical specificity. Calibrators must be commutable, a property that must be checked experimentally. It is possible to produce stable and commutable materials for the calibration of a set of methods. Interest of this approach has been demonstrated for several enzymes. Results of two studies presented here show that the comparison of results to the upper limit of reference ranges does not improve the interlaboratory comparability of results in contrast to the calibration of different methods by a common calibrator which allowed to reach an interlaboratory CV close to 4% for ALT and gammaGT.

[Plasma and saliva DST (dexamethasone suppression test) in depression. Clinical applications and kinetic approach]. / DST plasmatique et salivaire dans la dépression. Applications cliniques et approche cinétique.

Both plasmatic and salivary DST were simultaneously performed on a sample of 37 patients with a diagnosis of major depressive disorder (DMS III criteria): 22 primary depressions and 15 secondary depressions. Salivary DST showed a similar specificity but a decreased sensitivity in comparison with plasmatic DST. Essentially, the simultaneous use of both tests resulted in a better specificity for primary depression.

Thyroid function at the third trimester of pregnancy in a Northern French population.

OBJECTIVES: During pregnancy, the production rate of thyroid hormone increases when iodine intake is sufficient. However, the appropriateness of the free thyroxin (FT4) immunoassay is questionable. We have therefore evaluated prospectively the thyroid function in pregnancy and the relevance of the FT4 immunoassay. PATIENTS AND METHODS: The thyroid function of 114 pregnant, healthy Parisian women with mild iodine deficiency was studied at the third trimester of pregnancy, 55 of whom served as their own control three months after delivery, and the results were compared to North American reference values. RESULTS: All French pregnant women showed an increase in thyroxin binding globulin (TBG) serum levels. FT4 levels decreased by about 30% at the third trimester of pregnancy, as compared to 10-15% in the American population. Moreover, the increase in total thyroxin (TT4) secretion represented only 27%, as compared to 50% in the American population. Linear regression model analysis showed a positive correlation between levels of TT4 and TBG, TT4 and FT4, as well as FT4 and free thyroxin index (FTI). CONCLUSION: The hypothyroxinemia at the third trimester of pregnancy was more prominent in the Parisian population and insufficient iodine intake could be responsible for the deficient increase in TT4. It is therefore concluded that the inability of the thyroid to establish the required equilibrium could be corrected by systematic iodine supplementation before pregnancy. Finally, the strong correlation between FT4 and FTI suggests that the quality of FT4 test immunoassay is appropriate for estimating FT4 serum levels during pregnancy.

Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C.

BACKGROUND: Insulin resistance is a frequent feature of chronic hepatitis C. Whether insulin resistance could be the cause or consequence of steatosis and fibrosis is unknown. The ability of HCV genotype 3 to promote steatosis by itself provides an unique opportunity to answer this question. AIMS: The aim of the present study was to assess the relationships between insulin resistance, steatosis, and fibrosis according to genotype in 141 non-diabetic patients with biopsy proven non-cirrhotic chronic hepatitis C. METHODS: All patients had fasting serum glycaemia and insulinaemia measurements. Insulin resistance was evaluated using the homeostasis model assessment (HOMA IR) method. Liver steatosis was determined according to hepatitis C virus genotype (1 or 3). Logistic regression and multivariate regression analysis were used to identify variables independently associated with insulin resistance, fatty liver, and fibrosis. RESULTS: Although steatosis and fibrosis were more severe in genotype 3 patients, median HOMA IR was significantly higher in patients with genotype 1 related steatosis than in those with genotype 3 related steatosis (2.1 v 1; p = 0.001). Independent risk factors for steatosis were insulin resistance in genotype 1 patients (p = 0.001) and viral load in genotype 3 patients (p = 0.003). Among genotype 1 patients, independent parameters associated with insulin resistance were age (p = 0.04) and steatosis (p = 0.004). Steatosis was associated with more severe fibrosis whatever the genotype (p = 0.002). Among genotype 1 patients, although there was a significant relationship between circulating insulin level and fibrosis stage (p = 0.006), only steatosis and inflammatory score were independently associated with fibrosis. CONCLUSION: This study shows that insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients and that increased circulating insulin is a risk factor for fibrosis through insulin resistance induced steatosis.

[Hepatic fibrosis: physiopathology and biological diagnosis]. / Fibrose hépatique: physiopathologie et diagnostic biologique.

Hepatic fibrosis, of which cirrhosis is the most advanced stage, can result from any chronic liver disease due to any cause. Normal extracellular matrix components accumulate in the liver as a result of imbalances in their production, deposition, and breakdown. These matrix components are produced primarily by myofibroblastic hepatic cells whose main cellular source in the liver is the stellate cell (Ito cell). Histopathological examination of a liver biopsy specimen is currently the gold-standard investigation for estimating the severity of fibrosis in patients with chronic liver disease. However, the recent development of treatments with activity against the fibrosing process requires evaluation of fibrosis at closely spaced intervals and, therefore, the development of tests that do not require a liver biopsy. Advances in our understanding of the mechanisms underlying hepatic fibrogenesis have allowed to identify several substances of potential clinical usefulness. Serum assays of extracellular matrix components, their breakdown products, or enzymes involved in their metabolism have been suggested for the noninvasive evaluation of hepatic fibrosis. Clinical studies have shown that serum hyaluronate is to date the marker with the closest correlations to hepatic fibrosis and the noninvasive parameter with the highest sensitivity for cirrhosis.

Predictive factors in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: role of serum markers of connective tissue.

The aim of this study was to define factors predictive of the onset of the terminal phase, defined by hyperbilirubinemia or the occurrence of a severe clinical complication, in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. The 97 primary biliary cirrhosis patients in this study participated in a 2-yr clinical trial. Four of the 49 patients treated with ursodeoxycholic acid (13 to 15 mg/kg/day) entered the terminal phase of the disease, compared with 9 of the 48 patients assigned to placebo. In addition to clinical, conventional biological and histological parameters, we analyzed three serum markers of connective tissue components--type III procollagen aminoterminal peptide, hyaluronic acid and laminin. In the ursodeoxycholic acid-treated group, hyaluronic acid, type III procollagen aminoterminal peptide, bilirubin and splenomegaly were the factors most closely associated with entry into the terminal phase of the disease. In multivariate analysis, after adjustment for age, the hyaluronic acid level was the only predictive factor. In the placebo-treated group, the bilirubin level, total bile acid level, Mayo score, type III procollagen aminoterminal peptide, hyaluronic acid, splenomegaly and pruritus were associated with aggravation of disease. In multivariate analysis, high bilirubin level, high type III procollagen aminoterminal peptide or hyaluronic acid levels and low prothrombin time independently implied poor prognosis. In conclusion, when patients with primary biliary cirrhosis are treated with ursodeoxycholic acid, bilirubinemia loses, in part, its predictive value. It is replaced by hyaluronic acid and type III procollagen aminoterminal peptide. This suggests that models used in deciding on the need for liver transplantation require adaptation for patients receiving ursodeoxycholic acid.

Effect of dihydrotestosterone on the rate of ethanol elimination in healthy men.

Testosterone (T) and, more potently, dihydrotestosterone (DHT), are in vitro inhibitors of hepatic alcohol dehydrogenase (ADH). An increase in the rate of ethanol disappearance (RED) in man has been observed after orchidectomy. We thus investigated the influence of DHT administration on RED in 10 healthy male volunteers. RED was estimated after an oral ethanol bolus (0.6 g/kg), before and after a 14-day treatment with DHT (2 x 125 mg per day percutaneously; Andractim, Besins iscovesco, France). A mean 11.5-fold increase in DHT levels and a 2.0-fold decrease in T values were observed after DHT administration, confirming the good compliance with treatment. RED was decreased after DHT (0.168 +/- 0.043 vs. 0.137 +/- 0.043 g/l/hr; mean +/- SD; p less than 0.01 using Wilcoxon's paired comparison test). These data are consistent with a DHT-induced inhibition of hepatic ADH in vivo. This could have a beneficial effect by decreasing acetaldehyde production in alcoholic patients, in whom marked hypoandrogenism frequently occurs.