Search PubMed⌕ Search

Biomedical subjects

L Nicod

Publications and source records attributed to L Nicod.

At least 37 records · Page 2Linked to original sources
PubMed1999

Treatment of cachexia with recombinant growth hormone in a patient before lung transplantation: a case report.

OBJECTIVES: To describe the effects of recombinant human growth hormone (rhGH) in a severely malnourished patient before lung transplantation. DESIGN: Case study. SETTING: Intensive care unit. PATIENTS: A 38-yr-old severely malnourished (body mass index, 15.1 kg/m2) woman (receiving prednisone) with bronchiolitis obliterans evolving during 10 yrs presented with end-stage lung disease and required continuous noninvasive mechanical ventilation. INTERVENTIONS: Two courses of 35 days of 16 IU/day (0.42 IU/kg/day) rhGH administered subcutaneously, with an interruption of 5 wks between the two courses of rhGH. MEASUREMENTS AND MAIN RESULTS: Weight gain of 14.7% and 12.8% fat-free mass, as measured by 50-kHz bioelectrical impedance analysis, during treatment during a 3.5-month period. Nitrogen excretion decreased from 23.7 g/day before treatment to 8.0 g/day while receiving rhGH. Improvement of pulmonary function was also noted and allowed discharge of the patient from the hospital after the second course of rhGH. She underwent successful lung transplantation 2 months later and reached 48.8 kg of body weight 6 months later. CONCLUSIONS: rhGH treatment is a possible strategy that could be used with malnourished patients who are awaiting lung transplantation to improve the nutritional status and respiratory muscle function to prevent recurring respiratory infection and postoperative complications favored by malnutrition and possibly to decrease the length of hospital stay.

Adult↗
PubMed1998

Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.

A new isolating procedure of human hepatocytes has been developed using two-step collagenase digestion by a non-perfusion procedure (NP) of non-wedge liver biopsies. 1. A yield of 2-7 x 10(6) hepatocytes/g liver, 52-95% viability and 13-75% attachment were obtained from liver biopsies weighing 6-60 g, comparable to that obtained when using the classical perfusion procedure (P) to isolate human hepatocytes from wedge liver samples of 50-150 g. 2. In culture, human hepatocytes obtained by NP remained attached to plastic for up to 5 days and displayed the usual morphological characteristics. Their metabolic capacities, assessed by liver-specific albumin and urea synthesis and by CYP-dependent and conjugation pathways, were equivalent to those of human hepatocytes obtained by P. In addition, they responded adequately to specific CYP inducers, demonstrating that they constitute a model in which human drug metabolism and toxicity studies can be performed.

Adult↗
PubMed1998

Successful combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas.

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiolipomas are rare but distinct clinical entities that share similar morphological features. Lung transplantation is considered as a valuable therapeutic modality in patients with end-stage pulmonary LAM. However, in some patients, renal complications due to bleeding angiomyolipomas and cyclosporin-induced nephropathy have become newly identified problems. This study reports the first case of combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas. Two years after transplantation, renal and pulmonary function have remained stable and the patient has resumed a normal daily life, including a full-time professional activity.

Adult↗
PubMed1997

Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells.

Acetaminophen (APAP) induced a concentration-dependent (0-30 mM) cytotoxic effect in human HepG2 hepatoma cells which was significantly increased when intracellular reduced glutathione (GSH) content was decreased. The cytotoxic effect of APAP (0-30 mM) was significantly lower in a day 3-treated compared to day 1-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 5 microM 3-methylcholanthrene (3MC), 50 microM rifampicin (RFP) or 1 mM isoniazid (INH) significantly increased 15-30 mM APAP cytotoxicity, of about 15-20% for INH and RFP and 35-50% for 3MC. The cytotoxicity of 10 mM APAP was also increased (about 20%) by a 3-day preincubation with INH but was not affected by 3MC and RFP. INH induced a concentration-dependent (0-40 mM) cytotoxic effect in day-1 treated HepG2 cells and not significantly affected by decreases in intracellular GSH concentrations. INH was not cytotoxic in day 3-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 50 mM RFP or 1 mM INH significantly increased 10-40 mM INH cytotoxicity, respectively of about 10% and 10-25%. A 3-day preincubation with 3MC did not modify the cytotoxic effect of INH at these concentrations. This is to our knowledge the first report of increases by INH and RFP of APAP of INH cytotoxicity in vitro in hepatocellular cells of human origin. It is in accordance with clinical observations of severe hepatotoxicity associated with APAP or INH usage in patients receiving multiple drug therapy (INH, RFP) for tuberculosis or in alcoholics.

Acetaminophen↗
PubMed1997

End-stage cystic fibrosis: improved diabetes control 2 years after successful isolated pancreatic cell and double-lung transplantation.

Over a period of years, insulin-dependent diabetes and respiratory insufficiency developed in a 35-year-old patient with end-stage cystic fibrosis. After waiting more than 4 years while receiving maintenance treatment with continuous liquid O2 and nasal ventilation, the patient underwent double-lung and pancreatic islet cell transplantation. Subsequently, the patient has enjoyed a normal life with full employment and much better control of his diabetes. Pancreatic islet cell transplantation is a simple and innocuous technique easily added to the end of lung transplantation. These new pancreatic cells, although locally injected, are still secreting more than 2 years later as assessed by repeated C-peptide measurements.

Acute Disease↗
PubMed1996

Relationship between pulmonary oxygen consumption, lung inflammation, and calculated venous admixture in patients with acute lung injury.

OBJECTIVE: To determine in patients with acute lung injury whether increased pulmonary oxygen consumption (VO2pulm), computed as the difference between oxygen consumption measured by indirect calorimetry (VO2meas) and calculated by the reverse Fick method (VO2Fick), would: (1) correlate with the degree of lung inflammation assessed by bronchoalveolar lavage (BAL); (2) lead to an overestimation of calculated venous admixture (Qva/Qt). DESIGN: Prospective study. SETTING: University hospital, medical intensive care unit. INTERVENTION: None. MEASUREMENTS AND RESULTS: In nine mechanically ventilated patients with acute lung injury (Apache II 12 +/- 5, lung injury score 2 +/- 0.6, mean +/- SD), whole-body VO2 (VO2wb) was determined simultaneously by indirect calorimetry and the reverse Fick technique, after which BAL was immediately performed. VO2meas was significantly higher than VO2Fick (128 +/- 24 and 102 +/- 18 ml/min per m2, respectively, p < 0.001). Median VO2pulm was 25.3 ml/min per m2 (range 1.98-51.5), thus representing 19 +/- 11% of VO2wb. Total BAL cellularity was increased in all patients (median 47, range 24-200 x 10(4)/ml), as was the total polymorphonuclear (PMN) count (median 78 range 5-93 x 10(4)/ml). Macrophage counts were in the normal range. There were raised BAL levels of interleukin-6 (IL-6) (median 945, range 23-1800 ng/ml) and elastase (median 391, range 5-949 ng/ml). Median protein levels were 270 micrograms/ml (range 50-505). There was no correlation between VO2pulm and BAL cellularity, PMNs, elastase, IL-6, or protein. Qva/Qt was 31.7 +/- 8%. Qva/Qt, corrected for the presence of VO2pulm, (Qva/Qtcorr), was 30.3 +/- 8% (P < 0.01 vs Qva/Qt), a 4.2% overestimation due to VO2plum. There was no correlation between Qva/Qt or Qva/Qtcorr and VO2pulm. CONCLUSIONS: In mechanically ventilated patients with acute lung injury, VO2pulm was increased and led to a 19% underestimation of VO2wb determined by the reverse Fick method, as well as to a 4.2% overestimation of calculated Qva/Qt. Lung inflammatory activity was increased, as assessed by BAL cellularity, IL-6 and elastase levels. However, there was no correlation between VO2pulm and the intensity of pulmonary inflammation.

Adult↗
PubMed1996

Auditory stress induces changes in membrane functions of mouse peritoneal macrophages.

Stressful events induce responses in the endocrine and immune systems. The authors analysed the influence of repetitive noise stress on peritoneal macrophage oxidative and phagocytic responses. Plasma corticosterone levels were also measured. Different groups of 6- to 8-week-old C57BL/6 male mice were exposed for 1 night (n = 14) and 3 nights (n = 21) to a sound stress of 110 dB in an audiogenic stress chamber. Control animals were submitted to a sham stress for 1 night (n = 13) and 3 nights (n = 17). A marked decrease was observed in the phagocytic response to yeast (P = 3 x 10(-4)) while a mild increase in the oxidative response stimulated by opsonized zymosan was noted only after the 3 night stress (P = 0.02). Corticosterone levels of control and stressed mice did not differ. These results indicate that the stress resulting from repetitive noise causes modifications in peritoneal macrophage activity, and that these changes are dependent on the duration of stress. These functional alterations seem more complex than a simple general suppression or activation.

Animals↗
PubMed1996

Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome.

Intraalveolar fibrin deposition is a typical finding in acute lung injury and is not necessarily harmful. However, persistence of intraalveolar fibrin deposit may lead to hyaline membrane formation and subsequent alveolar fibrosis, a histologic hallmark of late stages of acute respiratory distress syndrome (ARDS). Thus, timing of the intraalveolar clotting disorder seems to be critical. To explore the time course of factors contributing to fibrin deposition and resolution, we sequentially analyzed procoagulant activity and fibrin degradation (by D dimer) in bronchoalveolar lavage (BAL) fluid of patients developing ARDS and those at risk for, but finally not developing, the syndrome. A total of 36 bronchoalveolar lavages were performed in 11 patients developing ARDS and 15 lavages in 10 patients at risk for but not developing this syndrome. All patients were admitted to the intensive care unit for the treatment of sepsis, trauma, or shock. In early phases of ARDS, the procoagulant activity (PCA) in BAL was significantly higher than in the patients at risk, 320 +/- 83 U (mean +/- SEM) versus 50 +/- 25 U, p < 0.05. A similar difference was noted in subacute stages (280 +/- 91 versus 46 +/- 16 U, p < 0.05). In early ARDS we observed higher levels of D dimer in BAL than in patients at risk: 1,841 +/- 827 versus 293 +/- 134 ng/ml, p < 0.05. Similarly, values of D dimer in the subacute phase were 2,776 +/- 836 versus 237 +/- 125 ng/ml, p < 0.05. In ARDS as well as in the at-risk group, D dimer in BAL fluid showed good correlation with the polymorphonuclear leukocyte count and with protein content of BAL. There was no correlation between plasma and BAL levels of D dimer. We conclude that in ARDS both the procoagulant pathway and the fibrin degradation are markedly activated compared with these in patients at risk but finally not developing this syndrome. These findings expand our understanding of intraalveolar coagulation abnormalities by providing evidence of increased fibrin breakdown in this syndrome.

Acute Disease↗
PubMed1996

Matrix metalloproteinases and TIMP in acute respiratory distress syndrome.

To investigate the implication of extracellular matrix proteinases in acute respiratory distress syndrome (ARDS), we determined 92 kD gelatinase (92 G'ase) and its natural antagonist, the tissue inhibitor of metalloproteinases-1 (TIMP) in bronchoalveolar lavage fluid (BALF) and plasma of 33 intensive care unit (ICU) patients presenting with trauma or septic shock. Eleven of these patients developed short-course ARDS, nine developed prolonged ARDS, and 13 did not progress to ARDS. Ten non-ICU patients served as controls. During the early phase of disease, 92 G'ase in BALF of ICU patients was higher than in controls, but plasma levels were not different. TIMP was increased in BALF and plasma in ARDS as compared with those of patients at risk. The 92 G'ase/TIMP ratio in BALF remained elevated in late phases of prolonged ARDS. The high intrapulmonary levels of 92 G'ase in patients at risk and with ARDS may reflect increased turnover of extracellular matrix in acute lung injury. Increased TIMP may interfere with tissue repair and fibrosis by its inhibition of 92 G'ase. Interleukin-6 (IL-6) could be involved in enhanced local synthesis of TIMP. The balance between 92 G'ase and TIMP may play an important role in lung remodeling, which is characteristic of ARDS.

Adult↗
PubMed1996

Combined islet-lung transplantation in a cystic fibrosis patient.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.

Adult↗
PubMed1995

Adult and paediatric size bronchoscopes for bronchoalveolar lavage in mechanically ventilated patients: yield and side effects.

BACKGROUND: Bronchoalveolar lavage is considered a safe procedure. When performed in the mechanically ventilated patient, however, potentially harmful effects on respiratory and haemodynamic functions have been reported in which the size of the bronchoscope may play a part. Two different size bronchoscopes (adult and paediatric) were therefore investigated with regard to bronchoalveolar lavage yield and side effects. METHODS: Twenty mechanically ventilated patients underwent bronchoalveolar lavage with both adult and paediatric bronchoscopes in a randomised sequential manner. RESULTS: In a total of 45 pairs of bronchoalveolar lavage procedures no difference was noted between adult and paediatric bronchoscopes with regard to total cell yield, differential cell count, and microbiological results. Peak intratracheal pressure increased with the adult bronchoscope only. Systemic arterial pressures increased more with the adult than with the paediatric bronchoscope. PaO2 decreased with the adult but not with the paediatric bronchoscope. CONCLUSIONS: The paediatric bronchoscope offers a comparable bronchoalveolar lavage yield in mechanically ventilated patients to the adult bronchoscope, while the respiratory and haemodynamic side effects are significantly lower than with the adult size instrument.

Bronchoalveolar Lavage Fluid↗
PubMed1994

1,25-dihydroxyvitamin D3 dissociates production of interstitial collagenase and 92-kDa gelatinase in human mononuclear phagocytes.

To study the effect of mononuclear cell differentiation on metalloproteinase production, the human monocytic cell lines U937 and THP-1 were exposed to two well known differentiating agents, the phorbol esters (phorbol myristate acetate (PMA)) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). With U937 cells, PMA-induced differentiation increased the production of both interstitial collagenase and 92-kDa gelatinase, whereas exposure to 1,25-(OH)2D3 induced full interstitial collagenase expression in the absence of any detectable 92-kDa gelatinase production. In fact, when U937 cells were differentiated with PMA and then exposed to vitamin D3, the hormone actually suppressed phorbol-induced 92-kDa gelatinase biosynthesis. With THP-1 cells, PMA also induced the production of 92-kDa gelatinase fully, but unlike U937 cells, the combination of PMA and 1,25-(OH)2D3 was required for substantial interstitial collagenase biosynthesis. As with U937 cells, the addition of 1,25-(OH)2D3 to PMA-differentiated THP-1 cells caused a dose-dependent inhibition of 92-kDa gelatinase production. Northern hybridizations demonstrated that both phorbol esters and vitamin D3 act on monocytic cell lines at a pretranslational level. To determine whether metalloproteinase biosynthesis in normal differentiated mononuclear phagocytes was also modified by 1,25-(OH)2D3, human blood monocytes and alveolar macrophages were exposed to this hormone. In both cell types, basal and Staphylococcal-stimulated 92-kDa gelatinase production was markedly inhibited by 1,25-(OH)2D3. In contrast, interstitial collagenase production was completely unaffected by the hormone. In summary, the two major metalloproteinases produced by monocytic cells are regulated via distinct molecular pathways by the action of PMA and 1,25-(OH)2D3. Furthermore, vitamin D3 completely dissociates the production of 92-kDa gelatinase and interstitial collagenase in human mononuclear phagocytes.

Calcifediol↗
PubMed1994

Cerebral tuberculosis in the immunocompetent host: 8 cases observed in Switzerland.

8 cases of cerebral tuberculosis were observed between January 1985 and June 1993 at the University Hospitals of Lausanne and Geneva, Switzerland. 5 patients were foreigners and 3 were Swiss, 2 of them alcoholics. All patients were HIV seronegative. Mycobacterium tuberculosis was isolated in 7 patients and M. bovis in one patient. All patients had radiological or bacteriological signs of pulmonary tuberculosis, and 3 had miliary tuberculosis. 3 patients died, 5 were cured. The main prognostic factors were age and the degree of neurological impairment at the beginning of treatment. The epidemiological, clinical, diagnostic and therapeutic aspects of this rare and severe form of extrapulmonary tuberculosis are reviewed.

Adolescent↗
PubMed1994

Specific cellular and humoral immune responses induced by different antigen preparations of Echinococcus multilocularis metacestodes in patients with alveolar echinococcosis.

A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcus sp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multilocularis while humoral immune responses seem to predominate in E. granulosus infection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. multilocularis (EmcAg) as well as by two E. multilocularis specific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosus antigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularis specific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.

Adult↗
PubMed1994

Immunomodulatory agents: dioxothiadiazabicyclo[3.3.0]octanes and their 2-spiro derivatives.

A series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octanes and a series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octane 2-spiro derivatives were synthesized from L-(-)-R-cysteine ethyl ester in two steps. The synthetic route involved condensation of the amino acid with an appropriate aldehyde or ketone, then a further condensation of the resultant ethyl thiazolidine-4-carboxylate with an isocyanate or an isothiocyanate. The proliferative response to human lymphocyte mitogen (phytohemagglutinin) was used as a primary screening assay for most of the thiadiazabicyclic compounds in comparison with levamisole. Furthermore, the most active compounds were tested for ability to release soluble receptors (sRIL-2) after mitogenic stimulation of T cells and for ability to activate macrophage oxidative metabolism measured by chemiluminescence. Most compounds were active in all three tests and some showed dose-dependent activity.

Adjuvants, Immunologic↗
PubMed1993

Satellite PET and lung cancer: a prospective study in surgical patients.

Positron emission tomography (PET) appears to be an innovative method for imaging the proliferative activity of malignant tissue, in particular by means of 18F-labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was investigated in a satellite centre as an adjunct to conventional methods for estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of detection of lung cancer in candidates was determined prior to exploratory or therapeutic thoracotomy by FDG PET imaging. The study involved 36 patients with abnormal chest roentgenogram and suspected lung cancer who were due for thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively. Pulmonary malignancy was found in 31/36 patients and 29 had a focal increase in FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three of whom had a negative PET scan. The sensitivity of detection of lung cancer by FDG PET was therefore 93.5%. Bayesian study shows that FDG PET could be the most useful method in a population with a low prevalence of lung cancer. As illustrated by our study, a simple FDG PET scanning protocol in a satellite PET centre could provide adequate clinical information and help in deciding subsequent patient management.

Adenocarcinoma↗
PubMed1993

[Resurgence of a forgotten pathology: pylephlebitis caused by tuberculous adenopathies].

The incidence of abdominal tuberculosis represents less than 1% of all forms of tuberculosis. We report the case of a portal vein thrombosis associated with tuberculous adenopathy of the hepatic hilum discovered in a young woman free of symptoms, without any risk factors, who had recovered from a cavity pulmonary tuberculosis after a classical anti-tuberculous treatment. This case suggests that abdominal tuberculosis often remains undiagnosed. Reemergence of tuberculosis is likely because of the increase in the incidence of the acquired immunodeficiency syndrome.

Adult↗