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F Innocenti

Publications and source records attributed to F Innocenti.

At least 19 recordsLinked to original sources
PubMed2000

Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells.

The aim of the present study was to assess the cytotoxicity of manumycin, a specific inhibitor of farnesyl:protein transferase, as well as its effects on protein isoprenylation and kinase-dependent signal transduction in COLO320-DM human colon adenocarcinoma which harbours a wild-type K-ras gene. Immunoblot analysis of isolated cell membranes and total cellular lysates of COLO320-DM cells demonstrated that manumycin dose-dependently reduced p21 ras farnesylation with a 50% inhibitory concentration (IC50) of 2.51 +/- 0.11 microM and 2.68 +/- 0.20 microM, respectively, while the geranylgeranylation of p21 rhoA and p21rap1 was not affected. Manumycin dose-dependently inhibited (IC50 = 2.40 +/- 0.67 microM) the phosphorylation of the mitogen-activated protein kinase/extracellular-regulated kinase 2 (p42MAPK/ERK2), the main cytoplasmic effector of p21ras, as well as COLO320-DM cell growth (IC50 = 3.58 +/- 0.27 microM) without affecting the biosynthesis of cholesterol. Mevalonic acid (MVA, 100 microM), a substrate of the isoprenoid synthesis, was unable to protect COLO320-DM cells from manumycin cytotoxicity. Finally, manumycin 1-25 microM for 24-72 h induced oligonucleosomal fragmentation in a dose- and time-dependent manner and MVA did not protect COLO320-DM cells from undergoing DNA cleavage. The present findings indicate that the inhibition of p21ras processing and signal transduction by manumycin is associated with marked inhibition of cell proliferation and apoptosis in colon cancer cells and the effect on cell growth does not require the presence of a mutated ras gene for maximal expression of chemotherapeutic activity.

Alkyl and Aryl Transferases↗
PubMed1999

Metabolism of 6-mercaptopurine in the erythrocytes, liver, and kidney of rats during multiple-dose regimens.

PURPOSE: To describe the metabolism of 6-mercaptopurine (6-MP) in erythrocytes and tissues of rats after repeated administration of 6-MP at two dose levels and to provide evidence that in vivo modulation of 6-MP anabolism can be obtained by simultaneous treatment with ribavirin or hydroxyurea, two inhibitors of enzymes involved in the bioactivation of 6-MP to the active 6-thioguanine nucleotides (6-TGN). METHODS: Rats were treated i.p. with 6-MP at 12.5 and 25 mg/kg daily for 12 days and erythrocyte, liver, and kidney levels of 6-mercaptopurine nucleotides (6-MPN) and 6-TGN were investigated during the accumulation phase and for 50 days after the end of treatment. In combination studies, ribavirin at 75 and 100 mg/kg per day (for 6-MP, 25 and 12.5 mg/kg per day) or hydroxyurea at 200 mg/kg per day were given i.p. for 12 days. The measurements of thionucleotide levels in rat samples were performed by high-pressure liquid chromatography (HPLC). RESULTS: The maximal concentration (Cmax) and the area under the concentration versus time curve (AUC) of 6-MPN and 6-TGN in erythrocytes and tissues increased significantly after the administration of 6-MP at 25 mg/kg per day as compared with 12.5 mg/kg per day. In particular, the Cmax and AUC of 6-TGN in erythrocytes of rats treated with 6-MP at 25 mg/kg per day were approximately 5-fold higher than the 6-TGN values observed following treatment at 12.5 mg/kg per day. Moreover, 6-TGN levels in erythrocytes were significantly higher than those of 6-MPN (910.9+/-53.1 and 286.8+/-23.4 pmol/8 x 10(8) cells for 6-TGN and 6-MPN, respectively, P < 0.05) after treatment with 6-MP at 25 mg/kg per day. The administration of ribavirin, an inhibitor of inosine monophosphate dehydrogenase, in association with 6-MP increased the amount of 6-MPN detected in erythrocytes and tissues while reducing 6-TGN levels in samples. The production and accumulation of 6-MPN and 6-TGN were increased in erythrocytes and tissues by hydroxyurea, an inhibitor of ribonucleotide reductase. Finally, a significant correlation between thionucleotide concentrations and erythrocyte counts was observed. CONCLUSION: The overall results demonstrate that 6-MP is actively metabolized in rats and that its biotransformation can be modulated by agents acting on enzymes of the purine metabolism, resulting in significant changes in erythrocyte and tissue levels of 6-MPN and 6-TGN. These findings provide evidence that the rat is a suitable model for investigation of the metabolism of 6-MP and its possible pharmacologic modulation.

Animals↗
PubMed1999

Inhibitory effect of suramin in rat models of angiogenesis in vitro and in vivo.

The aim of the present study was to test the ability of the chemotherapeutic agent suramin to inhibit angiogenesis in experimental models in vitro and in vivo. In the culture of rat aortic rings on fibronectin, suramin dose-dependently inhibited vascular cell growth, achieving the maximal effect (mean - 88% versus controls, P < 0.05) at 400 microg/ml. Image analysis showed that suramin could inhibit microvessel sprouting in fibrin from rat aortic rings as evaluated by the ratio between the cellular area and the mean gray value of the sample (sprouting index); suramin at 50 microg/ml significantly reduced the sprouting index from the control value of 0.35+/-0.04 to 0.14+/-0.02 mm2/gray level (P < 0.05). Likewise, the area occupied by cells was 19.2+/-1.8 mm2 as compared with 41.8+/-4.2 mm2 in controls (P < 0.05). In the rat model of neovascularization induced in the cornea by chemical injury, suramin at 1.6 mg/eye per day reduced the length of blood vessels (0.7+/-0.1 mm as compared with 1.5+/-0.1 mm in controls, P < 0.05). In the same model the ratio between the area of blood vessels and the total area of the cornea (area fraction score) was decreased by suramin from 0.19+/-0.02 in controls to 0.03+/-0.003 (P < 0.05). Suramin given i.p. at 30 mg/ kg per day markedly inhibited the neovascularization induced in the rat mesentery by compound 48/80 or conditioned medium from cells secreting the angiogenic protein fibroblast growth factor-3 (FGF-3). The area fraction score in control rats treated with compound 48/80 was 0.31+/-0.03, and this was reduced to 0.07+/-0.01 by suramin (P < 0.05). After i.p. administration of FGF-3 the area fraction score was reduced by suramin from 0.29+/-0.03 to 0.05+/-0.01 (P < 0.05). These results provide evidence that suramin exerts inhibitory effects on angiogenesis in both in vitro and in vivo models.

Animals↗
PubMed1999

An improved HPLC method for therapeutic drug monitoring of daunorubicin, idarubicin, doxorubicin, epirubicin, and their 13-dihydro metabolites in human plasma.

A single high-performance liquid chromatography (HPLC) method, suitable for the analysis of daunorubicin, idarubicin, doxorubicin, epirubicin, and their 13-dihydro metabolites is validated in the present study. Preparation of plasma samples was performed by a first extraction of analytes with a chloroform/1-heptanol mixture (9:1) and reextraction with ortophosphoric acid 0.1 M. The chromatographic analysis was carried out by reversed-phase isocratic elution of anthracyclines with a Supelcosil LC-CN 5 mm column (25 cm x 4.6 mm internal diameter; Supelco) and detection was accomplished by spectrofluorimetry at excitation and emission wavelengths of 480 and 560 nm, respectively. All anthracyclines eluted within 15 minutes of injection and the method appeared to be specific, because the chromatographic assay did not show interferences at the retention time of analytes. The linearity, evaluated over a concentration range of 0.4-10,000 ng/mL, gave regression coefficients better than 0.999, with recoveries of doxorubicin-doxorubicinol and epirubicin-epirubicinol of 67%-109% and 61%-109% respectively, and 93%-109% for the other compounds. The limits of detection and quantification were 0.4 ng/mL in a 50-mL sample (40 pg/injection) for all anthracyclines tested. The method proved to be precise and accurate, as the within-day and between-day coefficients of variation were less than 10% and the accuracy of the assay was in the range of 91%-107%. Overall results indicate that it is feasible to analyze all the anthracyclines used in clinical practice and their major metabolites with a single optimized method, thereby simplifying their monitoring in chemotherapeutic regimens of cancer patients.

Antibiotics, Antineoplastic↗
PubMed1999

Respiratory muscle function and hypoxic ventilatory control in patients with type I diabetes.

STUDY OBJECTIVES: The interaction among pulmonary mechanics, respiratory muscle performance, and ventilatory control in subjects with insulin-dependent diabetes mellitus has so far received little attention. We therefore decided to assess the role of central factors and peripheral factors on the ventilatory response to a hypoxic stimulus in type I diabetic patients. SUBJECTS: Eight patients in stable condition aged 19 to 48 years old, with insulin-dependent diabetes mellitus (duration of the disease, 36 to 240 months) and no history of smoking, cardiopulmonary involvement, or autonomic neuropathy; and an age- and gender-matched control group. MEASUREMENTS: In each patient, we measured the following: pulmonary volumes; diffusing capacity of the lung for carbon monoxide (D(LCO)); time and volume components of ventilation (tidal volume [V(T)] and respiratory frequency); static compliance (Clstat) and dynamic compliance (Cldyn); swings in pleural pressure (Pes) and gastric pressure (Pg); and transdiaphragmatic pressure (Pdi), obtained by subtracting Pes from Pg. Maximal inspiratory Pes and Pdi during a maximal sniff maneuver were also measured. Swings in Pes and Pdi during V(T) as a percentage of Pes and Pdi during the maximal sniff maneuver [Pessw(%Pessn) and Pdisw(%Pdisn), respectively] were both considered as a measure of central respiratory output, and the Pessw(%Pessn)/V(T) ratio was considered as an index of neuroventilatory dissociation (NVD) of the inspiratory pump. Subjects were studied at baseline and during hypoxic rebreathing. RESULTS: Pulmonary volumes and D(LCO) were normal or slightly reduced. A lower Cldyn, higher central respiratory output, and NVD were found. During hypoxic rebreathing, patients had lower V(T), similar central respiratory output, and greater NVD per unit change in arterial oxygen saturation compared with values in control subjects. An increase in dynamic elastance, computed as 1/Cldyn, during hypoxia was found in patients, but not in normal subjects, and was directly related to concurrent changes in NVD. CONCLUSIONS: We have shown that the assessment of a normal Clstat and normal routine parameters of airway obstruction does not permit the definite exclusion of the role of peripheral airway involvement in insulin-dependent diabetes mellitus. Peripheral airway involvement is likely to influence indices of hypoxic ventilator) drive by modulating a normal central motor output into a rapid and shallow pattern of ventilatory response.

Adult↗
PubMed1999

Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with type I diabetes mellitus under good metabolic control.

Dyspnoea and pulmonary dysfunction have recently been associated with Type I (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary mechanics and of performance of inspiratory muscles in inducing dyspnoea has not been yet assessed in Type I diabetes. To better focus on this topic we evaluated nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and stable metabolic control, without a history of smoking and microvascular complications, alongside a group of 14 healthy control subjects. In each subject, pulmonary volumes, static and dynamic compliance, pleural pressure swings (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of respiratory muscle effort, and tension-time index [TTI=TI/TTOTxPplsw(%Pplsn)] were measured (TI=inspiratory time;TTOT=total time of the respiratory cycle). All subjects were studied at baseline and during hypoxic rebreathing. Patients had normal pulmonary volumes. During hypoxic rebreathing, a normal change in respiratory muscle effort [DeltaPplsw(%Pplsn)/DeltaSaO2] and DeltaTTI/DeltaSaO2, and a lower change in tidal volume versus change in oxygen saturation [DeltaVT(% vital capacity)/DeltaSaO2], resulted in a higher ratio of respiratory effort to tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified Borg scale, showed a greater rate of rise (DeltaBorg/DeltaSaO2) and a greater increase for a given level of respiratory effort in patients. Moreover, neuroventilatory dissociation related to the expression of peripheral airway involvement, as assessed in terms of low dynamic compliance, and to concurrent change in dyspnoea sensation. Patients with Type I diabetes mellitus under good metabolic control and with normal lung volumes may have abnormal peripheral airway function. The latter is thought to be responsible for the association between dyspnoea sensation and neuroventilatory dissociation.

Adult↗
PubMed1999

Immunohistochemistry applied to the study of bone marrow Gaucher's cells: a case report.

Gaucher's disease is frequently associated with immunologic abnormalities, e.g. hypergammaglobulinemia, polyclonal gammopathy and benign monoclonal gammopathy. A patient with Gaucher's disease and a selective accumulation of IgM k in Gaucher's cells without serum monoclonal gammopathies is described. The selective accumulation is detected by immunohistochemistry analysis performed on cryostat bone marrow biopsies.

Adult↗
PubMed1997

Chronic administration of suramin induces neurotoxicity in rats.

In the present study, the ability of suramin 18 mg/kg i.p. twice a week to induce chronic neurotoxicity in rats was investigated. After 20 weeks of suramin treatment, morphological analysis of nerve fibers demonstrated that 57.7+/-3.2% of them presented vesicular disruption of myelin sheaths; their thickness was 0.23+/-0.07 microm in suramin-treated rats with respect to 0.43+/-0.07 microm of controls (P<0.05). To investigate the interaction between suramin and nerve tissue, the binding of the drug to partially purified myelin P0 protein obtained from sciatic nerves was analysed. The percentage of suramin bound to rat myelin P0 protein was 94.0+/-9.5%; this value was decreased to 55.0+/-7.6% when heparan sulfate was added to the myelin protein suspension before suramin. The analysis of tissue drug concentrations at 5, 10 and 20 weeks of treatment showed that suramin accumulated into the sciatic nerve in a time-dependent fashion (130.8+/-18.1, 219.7+/-17.1 and 449.3+/-15.6 microg/g of tissue, respectively). In conclusion, suramin induces a chronic peripheral neurotoxicity in rats characterized by myelin damage and high tissue levels of the drug. The high affinity of suramin for partially purified myelin P0 protein suggests a possible mechanism for drug-induced toxicity.

Action Potentials↗
PubMed1997

Transthoracic three-dimensional echocardiographic reconstruction of left and right ventricles: in vitro validation and comparison with magnetic resonance imaging.

Two-dimensional (2D) echocardiographic and angiographic measurements of ventricular volumes are limited by geometric assumptions concerning cavity shape. We compared in vitro the accuracy of a three-dimensional (3D) echocardiographic system suitable for transthoracic imaging to magnetic resonance imaging (MRI) in the measurement of left and right ventricular volumes. Ventricular cast volumes from 14 excised formalin-fixed sheep hearts filled with an agarose solution were compared with data derived from 3D echocardiography and MRI. Left and right ventricular volumes from 3D echocardiographic reconstructions agreed well with actual volumes without significant underestimation or overestimation. MRI progressively underestimated left ventricular volumes as these increased and systematically underestimated right ventricular volumes. Our echocardiographic system designed for 3D transthoracic imaging combines excellent measurements of left and right ventricular volumes and the computed reconstruction of tomographic slices with the full spatial resolution of the original 2D images. Thus in this in vitro model, 3D echocardiography exhibited greater accuracy than MRI.

Animals↗
PubMed1997

Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel over 3 hours with a fixed dose of epirubicin, to investigate the plasma pharmacokinetics of this combination, and to evaluate the toxicity and the activity in previously untreated metastatic breast cancer patients. PATIENTS AND METHODS: Fifty patients with metastatic breast cancer, measurable disease, and normal left ventricular ejection fraction (LVEF) were eligible. Epirubicin was administered as an intravenous (I.V.) bolus at the fixed dose of 90 mg/m2 before the infusion of paclitaxel over 3 hours. The initial dose of paclitaxel was 135 mg/m2 and was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT). Plasma pharmacokinetics of paclitaxel and epirubicin was performed at cycle 1 in at least two patients per dose level of paclitaxel (175 up to 225 mg/m2). RESULTS: The DLT of this combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The mean peak plasma concentration of paclitaxel ranged between 5.1 and 6.2 micromol/L at doses of 175 to 225 mg/m2. The concentration of epirubicinol decreased from 47.3 +/- 9.4 to 37.9 +/- 7.5 ng/mL in patients treated with paclitaxel 175 and 225 mg/m2. The most relevant toxicity was grade 4 neutropenia (61% of all courses). The pharmacokinetic data of paclitaxel, in particular the time above the threshold level of 0.05 micromol/L, were not significantly related to myelosuppression. Cardiac toxicity was mild: three patients (6%) developed mild congestive heart failure that was responsive to therapy. Among 49 assessable patients, 41 responses (84%; 95% confidence interval [CI], 70% to 92%) were observed, and nine (18%) of these were complete. CONCLUSION: Our study demonstrates that (1) the MTD is epirubicin 90 mg/m2 and paclitaxel 200 mg/m2; (2) no clear relationship exists between pharmacokinetic data of paclitaxel and myelosuppression, while the increase in the dose of paclitaxel is associated with a reduction in epirubicinol plasma levels; and (3) the association is feasible, with low cardiotoxicity, and has a high activity in metastatic breast cancer.

Adult↗
PubMed1996

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine and methotrexate.

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine (6-MP) and methotrexate (MTX) was investigated in patients as well as in rats and in HL-60 human leukemic cells. Ten children affected by acute lymphoblastic leukemia (ALL) in remission received daily doses of 6-MP given at 25 mg/m2 and i.v. infusion of high-dose MTX at 2 or 5 g/m2 once every other week. When 6-MP was given alone, the mean peak plasma concentration (Cmax) and area under the curve (AUC) of 6-MP were 72.5 ng/ml and 225.3 h ng ml(-1). Concurrent treatment with MTX at 2 or 5 g/m2 resulted in a mean increase of 108% and 121% in the Cmax and of 69% and 93% in the AUC, respectively. In rats treated with an oral dose of 6-MP at 75 mg/m2, MTX given i.p. at 5 g/m2 produced mean increases of 110% and 230% in the Cmax and AUC of 6-MP, respectively. In HL-60 human leukemic cells incubated with 6-MP at 250 ng/ml, the cumulative intracellular concentration of 6-thioguanine and 6-MP nucleotides was not significantly modified by treatment with 20 micrograms/ml of MTX. The present findings indicate that high-dose MTX enhances the bioavailability of 6-MP as evidenced by the observed increases in the plasma Cmax and AUC of 6-MP in humans and animals.

Adolescent↗
PubMed1996

A new protocol (MiCEP) for the treatment of intermediate or high-grade non-Hodgkin's lymphoma in the elderly.

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy. Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.

Aged↗
PubMed1995

Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the proliferation of human colon adenocarcinoma cell lines.

The activity of the synthetic somatostatin analogue SMS 201-995 was investigated in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines. The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/- 1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8 M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480 cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also evaluated. The treatment produced a synergistic antiproliferative effect against SW620 cells as compared to untreated cultures, with growth inhibition being -20.2 +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU ml-1, respectively, but did not increase the activity of SMS 201-995 against the SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells.

Adenocarcinoma↗
PubMed1995

Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice.

The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36 mg/kg) in mice were investigated in the present study. The analysis of drug concentrations by HPLC indicated that the plasma Cmax (13.0 +/- 3.1 and 25.7 +/- 2.8 micrograms/ml, respectively) were reached at the 2nd hr. The values of CL were low (0.06 and 0.1 ml/min, respectively), and t1/2 beta values of 3.0 and 3.7 hr were found, after 18 and 36 mg/kg, respectively. The highest tissue concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5 micrograms/g respectively), followed by the pancreas (39.3 +/- 9.9 micrograms/g) and the ovary (53.4 +/- 5.6 micrograms/g) after 18 and 36 mg/kg, respectively. In the case of the colic tissue, paclitaxel Cmax were 14.4 +/- 0.8 and 32.8 +/- 3.5 micrograms/g at the 3rd hr, respectively, with sustained drug levels still detectable 24 hr after treatment. Paclitaxel Cmax values of 12.7 +/- 3.0 and 53.4 +/- 5.6 micrograms/g were detected in the ovary after 18 and 36 mg/kg, respectively. The overall results provide evidence that, after intraperitoneal administration, paclitaxel concentrates in peritoneal organs; however, the intraperitoneal route does not prevent systemic drug exposure, allowing high and sustained levels of paclitaxel also in several extraperitoneal tissues.

Animals↗
PubMed1994

Indications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus.

Abnormalities of pulmonary function tests have been described in type 1 (insulin-dependent) diabetes mellitus (IDDM). To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex, age, and body mass index. Compared with controls, diabetic patients had a reduced forced vital capacity (FVC) (87.5 +/- 13.1% vs. 96.4 +/- 13.6% of the predicted; P = 0.03) and forced expiratory volume in 1 s (FEV1) (90.5 +/- 17.7% vs. 101.2 +/- 13.2% of the predicted; P = 0.02). While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests, those with altered urinary albumin excretion rate (AER > or = 20 micrograms/min; range 21-589) (n = 7) had a significantly lower pulmonary diffusion capacity (DLCO) than the 16 normoalbuminuric subjects (62.6 +/- 7.2% vs. 88.7 +/- 20.1% of the predicted; P = 0.01). Moreover, in the group of patients, DLCO was inversely related with AER (r = -0.43; P = 0.04). In conclusion, IDDM is characterised by reduced FVC and FEV1, while a significant decrease in DLCO may be considered as selectively associated with renal disease.

Adult↗