Hepatitis C virus-associated cryoglobulinaemicglomerulonephritis with delayed appearance ofmonoclonal cryoglobulinaemia.
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Cryoglobulinemia↗
Biomedical subjects
G Banfi
Publications and source records attributed to G Banfi.
Pepsinogens: physiology, pharmacology pathophysiology and exercise.
Human gastric mucosa contains aspartic proteinases that can be separated electrophoretically on the basis of their physical properties into two major groups: Pepsinogen I (PGA, PGI); and Pepsinogen II (PGC, PGII). Pepsinogens consist of a single polypeptide chain with molecular weight of approximately 42,000 Da. Pepsinogens are mainly synthesized and secreted by the gastric chief cells of the human stomach before being converted into the proteolytic enzyme pepsin, which is crucial for the digestive processes in the stomach. Pepsinogen synthesis and secretion are regulated by positive and negative feed-back mechanisms. In the resting state pepsinogens are stored in granules, which inhibit further synthesis. After appropriate physiological or external chemical stimuli, pepsinogens are secreted in the stomach lumen where hydrochloric acid, secreted by the parietal cells, converts them into the corresponding active enzyme pepsins. The stimulus-secreting coupling mechanisms of pepsinogens appear to include at least two major pathways: one involving cAMP as a mediator, the other involving modification of intracellular Ca(2+)concentration. Physiological or external chemical stimuli acting through the intracellular metabolic adenyl cyclase are more effective in inducing ' de novo ' pepsinogen synthesis than those acting through intracellular Ca(2+). The activation of protein kinase C (PK-C) would appear to be involved in regulatory processes. The measurement of pepsinogens A and C in the serum is considered to be one of the non-invasive biochemical markers for monitoring peptic secretion and obtaining information on the gastric mucosa status of healthy subjects. Recently, pepsinogen measurements have been used as an effective biochemical method for evaluating and monitoring patients with gastrointestinal diseases and for checking the effects of drug treatment. The level of PGA in the serum is always high in normal gastritis, while in atrophic gastritis it is always low. In both cases the PGC level in the serum is high. In most gastrointestinal pathologies the ratio between the PGA/PGC decreases. Various reports concerning hormone and/or enzyme modification as well as gastrointestinal distress in the case of long distance exercise have been reported. It has been suggested that the origin of the gastrointestinal distress experienced by long distance runners is a transient ischaemia of the gastric mucosa; it is also suggested that a hypobaric-hypoxic environment could contribute to induce gastric mucosa necrosis. Interrelation between gastrointestinal distress, hypobaric-hypoxic environment and modifications of PGA and PGC, gastrin and cortisol was evaluated in 13 athletes after a marathon performed at 4300 m. Gastrointestinal symptoms occurred in approximately 40% of the athletes. After the race the athletes showed a significant increase of gastrin and cortisol, while the ratio between PGA/PGC decreased. No relationship was observed between gastrointestinal symptoms and hormonal changes after the race. A control group of five subjects, who had been exposed to the same environmental conditions, showed no gastrointestinal or hormonal alteration. Conversely, control subjects presented a significant decrease of cortisol related to the circadian rhythm. The same incidence of gastrointestinal symptoms at high altitude and at sea level and the absence of pathological alteration of PGA and PGC in the serum of the athletes indicates that running a marathon and living for 6 days at 4300 m does not induce gastric mucosa necrosis. Cortisol and gastrin alteration observed in the athletes at this altitude would seem to be related to an activation of the mesopontine and forebrain structures involved in the behavioural and metabolic integration of the autonomic control and arousal and psychophysical-exercise stress. 2000 Academic Press@p$hr
Altitude Sickness↗
Double recurrence of FSGS after two renal transplants with complete regression after plasmapheresis and ACE inhibitors.
A patient who had undergone a first cadaveric donor kidney transplantation for idiopathic focal segmental glomerular sclerosis (FSGS), had an immediate recurrence of a biopsy-proven FSGS that eventually led to graft failure within 5 years from transplantation. The patient underwent a second cadaveric transplantation 10 months later. An immediate recurrence of a biopsy-proven FSGS occurred that was treated with two protracted cycles of plasmapheresis of seven months each, with the addition of an ACE inhibitor from the beginning. A complete and stable remission of FSGS was observed, which continues after more than 6 years from the end of plasmapheresis. The recurrence of FSGS after a second transplantation has a poor prognosis, but prolonged plasmapheresis treatment, by removing circulating factors altering glomerular permselectivity, and the addition of ACE inhibitors, through their potential interference with TGF-beta, might be synergistic in obtaining permanent remission.
Adult↗
Comparative multicentre study of a panel of thyroid tests using different automated immunoassay platforms and specimens at high risk of antibody interference.
The introduction of automation for immunoassays in recent years has brought about important and evident improvements in assay precision. Increasing standardization and comparability between platforms should enable the development of clinical guidelines and diagnostic algorithms for appropriate clinical decision making. A continuing source of variation between different automated immunoassay platforms is the sporadic effect of interfering antibodies or substances, thus causing aberrant results not supporting the patient's clinical status. The aim of this study was to describe current thyroid panel variation between automated immunoassay platforms including population specimens at risk of antibody interference. A multisite design with laboratories in three different countries using four different automated immunoassay platforms (Roche-Boehringer Mannheim Elecsys (Italy), Roche-Boehringer Mannheim ES300 (Wales), Bayer Immuno 1 and the Bayer ACS:180 evaluated the thyroid panel of thyrotropin (TSH), triiodothyromine (T3), free thyroxine (FT4) and free triiodothyronine (FT3). A common set of 158 randomly selected patient samples of non-thyroid and thyroid disorders, with and without treatment, was tested. Included were 62 patient samples at risk for endogenous antibody interference with high antimicrosomal antibody, anti-TSH receptor antibody and increased rheumatoid factor sub-populations. Across all controls and between platforms, precision measurements were comparable and varied between 0.7% and 12.8% for TSH, 2.8% and 13% for FT4, 1.8% and 10.5% for FT3 and 3.1% and 16% for T3 assay. Acceptable correlation and reproducibility were found between the three Bayer Immuno 1 platforms at each country's site with all four thyroid panel assays demonstrating r-values of 0.989 to 1.000 and slopes of 0.915 to 1.078. Comparisons between the different platforms showed acceptable correlation for all thyroid panel assays. Specimens containing rheumatoid factor were associated with a significantly increased variation between systems for the FT4 and FT3 assays (p < 0.01). This effect did not appear to be selective for a given platform. For specimens with raised autoimmune antibodies and therefore at risk of assay antibody interference, no variation could be observed between the platforms.
Antibodies↗
External evaluation of LIAISON tumour marker assays on the fully automated chemiluminescent LIAISON immunoassay analyser.
The LIAISON immunoassay analyser was tested in a multicentre evaluation performed by 8 laboratories. The analytes evaluated were CA 15-3, CA 19-9, CA 125II, AFP, CEA, NSE and PSA. Excellent results were obtained for within-run and between-run precision with most assays showing within-run CVs < 5% and between-run CVs between 4 and 8%. The linearity of all assays was acceptable, however, for PSA, NSE and CA 19-9 a recovery > 110% was obtained for some of the samples tested. None of the assays revealed a high-dose hook effect. Method comparisons were performed by using the routine method of the respective study centre. Results generally showed an acceptable agreement between the LIAISON system and the different methods of comparison. The reference ranges for all assays were found to be in accordance with data known from the literature. All assays showed similar results for serum, heparinised plasma and EDTA plasma. Additionally, two experiments were performed with only one of the analytes tested: the sample-to-sample carry-over, using the CA 19-9 assay (3.3 x 10(-6)-2.3 x 10(-5)) and the functional sensitivity for the PSA assay (0.2 ng/ml).
Biomarkers, Tumor↗
Erythrocytes, haemoglobin and packed cell volume in athletes performing races in altitude environment.
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Adult↗
Clinical and prognostic value of serial renal biopsies in lupus nephritis.
Little information is available about the role of repeated renal biopsies in lupus nephritis. We analyzed retrospectively the prognostic significance of serial renal biopsies in patients with lupus nephritis. Thirty-one patients with lupus nephritis underwent two or more renal biopsies during follow-up. The indications for repeated biopsy were as follows: improvement of renal disease but persistence of nonnephrotic proteinuria (group A, 7 patients); persistent or relapsing nephrotic syndrome (group B, 12 patients); and worsening of renal function (group C, 19 patients). After a median follow-up of 10.5 years, 17 patients reached the end point (persistent doubling of plasma creatinine level). At repeated renal biopsy, there was a correlation between improved clinical and histological features for group A. In these patients, treatment was reduced or stopped successfully. Histological features remained almost unchanged in group B. All patients showed an improvement of proteinuria after reinforcement of therapy. In group C, the worsening of renal function was associated with a variable and clinically unpredictable combination of active and chronic lesions. Only the few patients with an elevated activity index and moderate chronicity index showed a favorable and persistent improvement of renal disease after reinforcement of therapy. At multivariate analysis of clinical and histological data at presentation, only male sex was predictive of an adverse outcome (P = 0.015). At repeated renal biopsy, crescents in more than 30% of glomeruli (P = 0.0009) and chronicity index of 5 or greater (P = 0.00006) were associated with the probability of reaching the end point at multivariate analysis. Repeated renal biopsy may be helpful for establishing the prognosis in patients with lupus nephritis, particularly in the presence of worsening of renal function.
Adolescent↗
Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?
Eighty nephrotic adults with focal segmental glomerulosclerosis (FSGS) and plasma creatinine lower than 3 mg/dL were given corticosteroids (53 patients) or immunosuppressive agents (27 patients) for a median of 16 and 75 weeks, respectively. Forty-two patients responded with complete remission (29 patients, 36%) or partial remission (13 patients, 16%). Twenty-six patients who did not respond were treated again. Two patients obtained complete remission and 13 partial remission. The probability of remission was associated with treatment with corticosteroids (P = 0.0001; RR, 3. 93; 95% CI, 2.00 to 7.72), absence of arterial hypertension (P = 0. 0023; RR, 2.59; 95% CI, 1.41 to 4.79), and a percentage of hyaline glomeruli lower than 5% (P = 0.0152; RR, 2.04; 95% CI, 1.15 to 3.64). The probability of being alive at 110 months without doubling of plasma creatinine was 69%. The risk of renal insufficiency was correlated with mesangial proliferation (P = 0.0025; RR, 5.50; 95% CI, 1.82 to 16.60) and with interstitial fibrosis (P = 0.0231; RR, 4. 44; 95% CI, 1.23 to 16.08) at initial biopsy. Considering partial or complete remission as a time-dependent variable, only the lack of remission (P = 0.0027; RR, 7.23; 95% CI, 1.98 to 26.33) and mesangial proliferation (P = 0.0069; RR, 4.59; 95% CI, 1.52 to 13. 88) were correlated with renal failure. Major side effects were observed in 11 patients (5 infections, 1 peptic ulcer, 2 diabetes, 3 neoplasias). This study shows that 70% of nephrotic adults with FSGS may obtain complete or partial remission and maintain stable renal function for about 10 years when given a prolonged therapy with corticosteroids or immunosuppressive drugs.
Adrenal Cortex Hormones↗
Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors.
UNLABELLED: We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.
Adenoma↗
A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.
To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.
AIDS-Related Opportunistic Infections↗
Treatment of membranous lupus nephritis.
In this study, we retrospectively analyzed the effects of treatment in 19 patients with membranous lupus nephritis (MLN) and nephrotic syndrome. Eight patients were treated with corticosteroids alone, and the other 11 patients received methylprednisolone and chlorambucil alternated every other month for 6 months. At presentation, sex, age, duration of renal disease before renal biopsy, plasma creatinine, and arterial hypertension were similar in the two study groups. Of the eight patients treated with corticosteroids alone, three showed complete remission and one partial remission of the nephrotic syndrome. During the follow-up (mean, 114+/-63 months), seven of these eight patients developed one or more renal flare-ups. Of the 11 patients treated with methylprednisolone and chlorambucil, seven had complete remission, and the other four had partial remission of the nephrotic syndrome. During the follow-up (mean, 83+/-59 months), only one patient had renal flare-up. At the end of the follow-up, all patients were alive, but three patients in the group treated with corticosteroids alone had developed a doubling of plasma creatinine, and another patient had persistent nephrotic syndrome. Two other patients were in complete remission, one patient was in partial remission, and the last patient had nonnephrotic proteinuria. In the group of patients treated with methylprednisolone and chlorambucil, one patient developed extracapillary glomerulonephritis and eventually entered end-stage renal failure 24 years after the clinical onset of renal disease. Seven patients were in complete remission, and three patients were in partial remission at the last follow-up visit. This retrospective study suggests that methylprednisolone and chlorambucil may induce a more stable remission of nephrotic syndrome and may better protect renal function in the long term in comparison with corticosteroids alone. However, these results must be confirmed by a prospective controlled trial.
Adolescent↗
End-inspiratory airway occlusion: a method to assess the pressure developed by inspiratory muscles in patients with acute lung injury undergoing pressure support.
We evaluated the end-inspiratory occlusion maneuver as a means to estimate the inspiratory effort during pressure support ventilation (PS). In nine nonobstructed acute lung injury (ALI) patients, we applied four levels of PS (0, 5, 10, 15 cm H2O) to modify the inspiratory effort. End inspiratory occlusions (2 to 3 s) were performed at the end of each experimental period by pushing the inspiratory hold button of the ventilator (Servo 900 C; Siemens, Berlin, Germany). We took the difference between the end-inspiratory occlusion plateau pressure and the airway pressure before the occlusion (PEEP + PS) as an estimate of the inspiratory effort and called it PMI (Pmusc,index). From the esophageal pressure tracing we obtained a reference measurement of the pressure developed by the inspiratory muscles at end inspiration (Pmusc,ei) and of the pressure-time product per breath (PTP/b) and per minute (PTP/min). In each patient, PMI was correlated with Pmusc,ei (p < 0.01) and PTP/b (p < 0.01). A PMI threshold of 6 cm H2O detected PTP/min < 125 cm H2O s/min with a sensitivity of 0.89 and a specificity of 0.89. We conclude that PMI is a good estimate of the pressure developed by the inspiratory muscles in ALI patients and may be used to titrate PS level. The major advantage of PMI is that it can be obtained from the ventilator display without any additional equipment.
Acute Disease↗
Automation of human sperm cell analysis by flow cytometry.
Semen sample analysis is routinely performed by microscopical evaluation and manual techniques by laboratory operators; the analysis is affected by a wide imprecision related to variability among observers, influencing its clinical validity. Our aim was to automate sperm analysis with the use of flow cytometry for evaluation of cell counts and typing and with the use of a new membrane-permeant nucleic acid stain for evaluation of sperm viability. Statistical analysis of the comparison between manual and automated methods for sperm counts was performed by the Bland and Altman method; the mean difference was 0.243 x 10(6) sperms/ mL. The precision of the flow cytometric analysis was evaluated with whole sperm; the between-run CV was 7.5% and the within-run CV was 2.5%. Data observed suggest that flow cytometric sperm analysis, with high precision and accuracy and low costs, can be proposed for routine use in clinical laboratories.
Adolescent↗
Prostate-specific antigen is not increased in young men by ultraendurance sport performances.
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Adolescent↗
Stability of tumor markers CA 19.9, CA 125, and CA 15.3 in serum obtained from plain tubes and tubes containing thixotropic gel separator.
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Biomarkers, Tumor↗
Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection.
This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear; NS may represent another manifestation of CMV disease.
Adrenal Cortex Hormones↗
Extracapillary glomerulonephritis and renal amyloidosis.
We report three patients with well-documented renal amyloidosis who developed rapidly progressive renal failure. Renal biopsies from all three patients showed crescentic glomerulonephritis imposed on renal amyloidosis. All patients were treated with intravenous high-dose methylprednisolone pulses combined with immunosuppressive agents and oral corticosteroids. Partial recovery of renal function was obtained in two patients. For the third patient, treatment had to be stopped after a few days because of a septic arthritis. Renal function continued to deteriorate, and the patient had to be placed on regular hemodialysis. We conclude that extracapillary glomerulonephritis may occasionally complicate a preexisting renal amyloidosis and may be reversible if recognized early and treated appropriately.
Aged↗
"Nephritic flares" are predictors of bad long-term renal outcome in lupus nephritis.
We retrospectively analyzed the courses of 70 patients with lupus nephritis followed for 5 to 30 years (median 127 months). Patients survival was 100% at 10 years and 86% at 20 years. The probability of not reaching the end point (persistent doubling of plasma creatinine) was 85% at 10 years and 72% at 20 years. A multivariate analysis of variables at presentation showed that male sex (P = 0.005) and hematocrit lower than 36% (P = 0.01) were associated with the end point (relative risk 7.5 and 14). We then analyzed for the role of renal flare-ups, defined either as a rapid increase in plasma creatinine or by an increase in proteinuria. Patients with renal flares of any type had more probabilities of reaching the end point than patients who never had flares (P = 0.03; relative risk 6.8). The hazard of the end point was 27 times higher in patients with flares along with rapid increased in plasma creatinine than in patients without flares or with flares with proteinuria alone (P < 0.00001). This hazard was higher when plasma creatinine did not return to the basal levels within two months after treatment (P < 0.00001).
Adult↗