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Biomedical subjects

M Giordano

Publications and source records attributed to M Giordano.

At least 109 records · Page 6Linked to original sources
PubMed1997

Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits the binding of N-formylmethionyl-leucyl-phenylalanine to neutrophil receptors.

Losartan, a selective antagonist of AT1 receptors for angiotensin II, is widely used clinically to manage hypertension. We report here that losartan markedly inhibits neutrophil shape change, adherence and chemiluminescence responses triggered by N-formylmethionyl-leucyl-phenylalanine (fMLP), without affecting responses induced by immune complexes, zymosan or concanavalin A. Neither saralasin, another antagonist of angiotensin II receptors, nor captopril, an angiotensin-converting enzyme inhibitor, reproduced the effects of losartan. It was also observed that neutrophil responses triggered by fMLP were not affected by exogenously added angiotensin II. The effect of losartan on the binding of fMLP was measured using [3H]fMLP. It was found that losartan inhibits the binding of [3H]fMLP to neutrophil receptors. As observed for neutrophils, studies performed with monocytes showed that losartan inhibits chemiluminescence emission triggered by fMLP, without affecting chemiluminescence responses triggered by immune complexes, zymosan or concanavalin A.

Angiotensin I↗
PubMed1997

[Rokitamycin in odontostomatology. Controlled study of doses].

BACKGROUND: Rokitamycin is a semisynthetic macrolide with a lactonic ring with 16 atoms, showing anti-bacterial action at concentrations near to MIC. A controlled clinical study is carried out, in parallel groups, whose aim was to assess the therapeutic action and safety of two dosage schemes of rokitamycin, in the short term treatment (5 days) of acute infective processes of odontostomatological origin. METHODS: Twenty patients (14 males, 6 females) were recruited for the trial, suffering from alveolitis, abscess, phlegmon, sialadenitis and suppurating cysts. The patients were divided in a randomized fashion into two groups: 10 patients were treated orally with 800 mg/day and 10 with 1200 mg/day. Rokitamycin was supplied in 400 mg tablets. RESULTS: The 5 days of treatment with rokitamycin determined the complete resolution of the infective process, with eradication of the germs originally isolated, all belonging to the Streptococcus genus. Clinical efficacy was evident by the third day of treatment, with a prompt improvement of symptoms (functional limitation, pain, tumefaction) and the return of body temperature to within normal limits, in a totally superimposable fashion between the two groups. Safety was excellent with both doses, with no side effects observed. CONCLUSIONS: The results of the study show that treatment with rokitamycin in the short term, at the usual dosage of 800 mg/day, is a valid therapeutic scheme in infective processes in odontostomatology.

Adolescent↗
PubMed1996

Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics--a phase II multicenter study.

PURPOSE: A Phase II multicenter trial testing an accelerated regimen of radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry-derived tumor potential doubling time (Tpot). METHODS AND MATERIALS: From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinomas of the oral cavity and the oropharynx, with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction once a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day, with a 6-h interval, one of the two fractions being delivered as a concomitant boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy), shortening the overall treatment time to 4.5 weeks. A contemporary control group of 46 patients with Tpot of >5 days or unknown was treated with conventional fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy. RESULTS: All patients completed the accelerated regimen according to protocol and in the prescribed overall treatment time. Immediate tolerance was fairly good: 65% of the patients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to persist longer in AF than in CF patients. The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of the AF patients was 49.4%, while actuarial 2-year overall survival for the same patients was 43.5%. CONCLUSION: The results suggested that this accelerated regimen is worth testing in a controlled randomized trial to compare different accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA flow cytometry technique as a suitable method of evaluating tumor cell kinetics in multicenter clinical studies, on condition that all measurements are carried out by one most experienced laboratory.

Adult↗
PubMed1996

Renal hemodynamics in renal transplant recipients. The role of reduced kidney mass and cyclosporine administration.

It has been hypothesized that both the cyclosporine (CsA) treatment and the reduction of renal mass may affect the renal hemodynamic regulation in kidney transplant recipients. To address this question, we evaluated the renal hemodynamic response to hyperaminoacidemia (i.v. mixed amino acid infusion 3.3 mg/kg/minute for 150 minutes) in four study groups: (1) 16 renal transplant recipients (Tx), (2) 6 uninephrectomized (Nx) subjects, (3) 7 subjects treated with CsA for chronic uveitis (CsA), and (4) 9 normal controls (NC). In response to amino acid administration (AA), glomerular filtration rate (GFR) rose significantly in NC subjects (80 +/- 6 vs. 91 +/- 6 ml/minute; P<0.01) and Nx patients (57 +/- 3 vs. 68 +/- 7 ml/minute; P<0.01) and failed to increase in Tx recipients (39 +/- 3 vs. 37 +/- 3 ml/minute) and CsA-treated patients (58 +/- 3 vs. 53 +/- 4 ml/minute). Renal plasma flow (RPF) did not change in Tx recipients (243 +/- 27 vs. 235 +/- 25 ml/minute) but rose significantly in all other groups (257 +/- 17 vs. 344 +/- 33 in NX, 364 +/- 6l vs. 441 +/- 55 in CsA, 412 +/- 49 vs. 472 +/- 72 ml/min in NC subjects; P<0.05 vs. basal). Basal renal vascular resistances were significantly higher in Tx (0.29 +/- 0.04 mmHg/mlxmin; P<0.01 vs. all other groups) than in Nx (0.21 +/- 0.01 mmHg/mlxmin), CsA (0.23 +/- 0.04 mmHg/mlxmin) (both P<0.01 vs. NC subjects), and NC subjects (0.13 +/- 0.02 mmHg/mlxmin). Renal vascular resistance failed to decline in Tx (0.31 +/- 0.04 mmHg/mlxmin) during AA infusion but declined significantly in all other groups. In Tx, basal GFR was positively correlated to renal allograft volume (r=0.547, P<0.03); however, no relationship was found between the latter and basal RPF or the AA induced changes in GFR. In summary, the present study demonstrates that in kidney transplant recipients and in CsA-treated subjects, the renal functional reserve to hyperaminoacidemia is impaired. This is at variance to what is observed in normal controls and uninephrectomized subjects. In renal transplant recipients, basal but not amino acid stimulated GFR correlates with renal allograft volume. We conclude that basal GFR is related to renal volume in Tx and that the response to hyperaminoacidemia seems to be affected by chronic CsA administration.

Adult↗
PubMed1996

Interactions between dopamine and GABA in the control of ambulatory activity.

Ambulatory activity of male rats was quantified in an open field. The subjects were treated with DL-amphetamine and amfonelic acid alone or combined with the GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate as well as with the GABAA agonist THIP and the GABAB agonist baclofen. Subeffective doses of the GABAergic drugs did not modify the effects of moderate doses of the dopaminergic stimulants whereas effective doses continued to reduce ambulatory activity just as in the absence of dopaminergic activation. When DL-amphetamine or amfonelic acid were administered in doses that strongly enhanced ambulatory activity, doses of the GABAergic drugs that were inhibitory in the absence of dopaminergic stimulation were no longer effective. The mixed D1/D2 dopamine antagonist pimozide, the D1 antagonist SCH 23390 and the D2 antagonist sulpiride were then combined with subeffective doses of the GABA agonists. GAG, sodium valproate and baclofen were potentiated by pimozide and SCH 23390 but not by sulpiride. THIP was ineffective. These data show that GABAergic drugs had a reduced effect after stimulation of dopaminergic neurotransmission. On the other hand, when dopamine D1 receptors were blocked, nonselective GABA agonists and the GABAB agonist baclofen were potentiated. This was not the case for the GABAA agonist THIP, suggesting that the GABAA receptor is of slight importance for the interactions between GABA and dopamine in the control of ambulatory activity. No potentiation of GABAergic agonists was obtained after treatment with a dopamine D2 antagonist.

4-Aminobutyrate Transaminase↗
PubMed1996

Short and long restraint differentially affect humoral and cellular immune functions.

The aim of this work was to examine the effect of different periods of restraint on the humoral and cellular immune functions in adult male rats. Short restraint stress (2 h over 2 consecutive days) enhanced the primary serum antibody response to sheep red blood cells. The enhancement of this humoral response was dependent on the restraint period, since long restraint stress (6 h over 4 days) failed to modify this response. Short and long restraint decreased both the number of lymphocytes and the T-lymphocyte response to Con A stimulation in the peripheral blood. Neither 2 h over 2 days nor 6 h over 4 days modified the splenic lymphoproliferative response to Con A stimulation, but restraint stress progressively decreased the number of mononuclear splenic cells. Both periods of restraint significantly increased plasma concentration of corticosterone, however plasma prolactin levels were significantly lower after 4 days of restraint but not after short restraint (2 h over 2 days). These results indicate that although some immune functions can be increased after acute or short stress, long stress has an immunosuppressive effect, above all on the cellular immunity which is more susceptible to this effect than the humoral response.

Animals↗
PubMed1996

Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH.

The role of nitric oxide in the regulation of adrenal steroidogenesis was examined in BALB/c mice by employing the nitric oxide synthase inhibitors NG-nitro L-arginine methyl ester (L-NAME) and NG-nitro L-arginine (L-NNA). The administration of a single dose of nitric oxide inhibitors (50 mg kg-1 body wt. i.p.) induced a fourfold increase in plasma corticosterone. Treatment with L-arginine (750 mg kg-1 body wt. s.c.), but not D-arginine, completely prevented corticosterone increases induced by L-NAME. To analyse whether the activation of adrenal steroidogenesis induced by nitric oxide synthase inhibitors involved the stimulation of the hypothalamo-pituitary-adrenal axis. ACTH levels were assessed. It was found that L-NAME significantly enhanced plasma ACTH concentrations. Genetic variations in this regulatory pathway are suggested by the fact that L-NAME increased corticosterone levels in BALB/c. C3H/He and DBA-2 mice, but not in C57BI/c mice, a strain characterized by a low steroid response to stress.

Adrenal Glands↗
PubMed1996

Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy.

RATIONALE: To establish relationship, if any, between renal morphology and renal haemodynamic response to amino acids. DESIGN AND METHODS: We investigated the correlation between renal haemodynamic regulation and morphology in a group of 15 patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1, GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42 ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided into two groups according to the histological staging of glomerular lesions: group I (n = 7) stage II, and group II (n = 8) stage III-IV. RESULTS: In the basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6 ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/- 0.01) (P < 0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/- 0.02). In order to evaluate the renal functional reserve, all study groups underwent to an intravenous amino-acid infusion designed to increase plasma amino acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls). In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/- 2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3% versus basal) (both P < 0.01 vs basal). In contrast, in patients with more severe glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/- 4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P < 0.01 versus group I and controls). CONCLUSIONS: The data show that in IgA nephropathy: severe forms of glomerular lesions are associated with a complex alteration of glomerular haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic response to hyperaminoacidaemia.

Adult↗
PubMed1996

Specific binding of 2-[125I]iodomelatonin by rat spleen crude membranes: day-night variations and effect of pinealectomy and continuous light exposure.

Melatonin binding sites were characterized in rat spleen crude membranes. The specific binding of 2-[125I]iodomelatonin by spleen crude membranes fulfills all the criteria for binding to a receptor site. Thus, binding was dependent on time and temperature, stable, specific, and increased under constant light exposure and after pinealectomy. In competition studies, the specific binding of 2-[125I]iodomelatonin to spleen crude membranes was inhibited by increasing concentrations of native melatonin. Scatchard analysis showed that the data were compatible with the existence of two classes of binding sites: a high affinity site with a Kd of 0.53 nM and a binding capacity of 2.52 pM, and a low-affinity site with a Kd of 374 nM and binding capacity of 820 pM. Moreover, binding of 2-[125I]iodomelatonin exhibited day-night variations with the highest binding observed late during the light period, and the lowest binding was observed late at night. However, binding of 2-[125I]iodomelatonin to membranes remained high when animals were kept under light exposure at night. Results support the hypothesis of a regulatory role of melatonin on the immune system in which melatonin downregulates its own binding site.

Animals↗
PubMed1996

Effect of alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists on renal function in hypertensive non-insulin-dependent diabetic patients.

In the present study we investigated the effect of a selective alpha 1-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (ACE) inhibitor (captopril), and a calcium channel antagonist (nifedipine) on renal function in hypertensive non-insulin-dependent diabetic patients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 +/- 1 kg/m2) (mean +/- SEM) were studied before and after a 12-week period of antihypertensive treatment. Ten patients were treated with doxazosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30-60 mg once daily). Blood pressure, creatinine clearance, 24-hour urinary protein excretion, fasting plasma glucose concentration and glycosylated hemoglobin were measured before and after drug treatment. Fasting plasma glucose and glycosylated hemoglobin (HbA1c) were similar in all three groups prior to the start of antihypertensive therapy and did not change significantly from baseline in any treatment groups. In the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 +/- 8 ml/1.73 m2.min (p < 0.01), while 24-hour urinary protein excretion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m2.min (p < 0.01). In diabetics treated with captopril creatinine clearance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m2.min (p < 0.05), while the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m2.min (p < 0.05). In patients treated with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m2.min), while 24-hour urinary protein excretion decreased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m2.min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril (153 +/- 3/93 +/- 1), and nifedipine (155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive therapy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p < 0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihypertensive agents caused a significant decline in proteinuria. These results indicate that alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists can safely and effectively be used in the clinical management of non-insulin-dependent diabetic patients with hypertension.

Adrenergic alpha-Antagonists↗
PubMed1996

Reassessment of the specificity of lens opacities in myotonic dystrophy.

Cataract has been considered for a long time one of the major indicators of the presence of the mutated myotonic dystrophy (DM) gene in asymptomatic relatives of DM patients. However, some recent studies show that not all cases of cataract typical of DM are associated with the disease even in members of DM families. In order to determine the frequency of lens opacities characteristic of DM in the general population and to evaluate the specificity of lens anomalies for detection of the DM premutation, we screened a sample of 1,400 random individuals for the presence of 'myotonic cataract'. Ten individuals were found with the typical lens opacities and no neuromuscular signs of DM; molecular analysis of the DM mutation showed that they all carried two normal alleles. Our data allow to conclude that bilateral cortical iridescent and posterior cortical lens opacities cannot be considered a marker of the presence of the DM premutation in the general population.

Adult↗
PubMed1996

Age of onset, sex, and cardiomyopathy as predictors of disability and survival in Friedreich's disease: a retrospective study on 119 patients.

We performed a retrospective study on a series of 119 of our patients who have Friedreich's disease to assess the predictive value of age at onset, gender, and left ventricular hypertrophy in regard to disease progression. Outcome variables were survival, time to loss of independent gait, and time to confinement in a wheelchair. Diabetes was considered to be an outcome variable when defining time to diabetes and an explanatory variable when testing its effect on survival. Eleven patients died. The median estimated survival from onset was 36 years, and the median time to loss of independent gait was 8 years and to confinement in a wheelchair was 15 years from onset. Nineteen patients developed diabetes after a median time of 16 years. The presence of left ventricular hypertrophy or diabetes significantly reduced survival based on univariate analysis. Onset at the age of < or = 20 years and the presence of left ventricular hypertrophy predicted a faster rate of progression of the disease.

Adolescent↗
PubMed1996

Differential responsiveness of protein synthesis and degradation to amino acid availability in humans.

We investigated the effects of graded hyperaminoacidemia on protein metabolism in eight healthy, young (25 +/- 2 years), normal weight (BMI = 25 +/- 1 kg/m2), overnight-fasted human subjects. A balanced amino acid solution was infused for 180 min at five different rates: 0.5 (study I), 1.0 (study II), 2.0 (study III), 4.0 (study IV). and 6.0 (study V) mg x kg-1 x min-1 on separate days in random order. Studies were performed with [1-14C]leucine infusion and indirect calorimetry to calculate leucine oxidation (LOX), nonoxidative leucine disposal (NOLD) (an index of protein synthesis), and endogenous leucine flux (ELF) (an index of proteolysis). Basal total plasma amino acid concentrations averaged 1.85 +/- 0.1 mmol/l and increased to 2.27 +/- 0.1, 2.70 +/- 0.2, 3.84 +/- 0.2, 5.87 +/- 0.4, and 7.52 +/- 0.3 mmol/l in studies I-V, respectively. ELF decreased from a basal value of 2.27 +/- 0.2 to 2.12 +/- 0.2, 1.97 +/- 0.1, 1.73 +/- 0.2, 1.67 +/- 0.3, and 1.65 +/- 0.1 micromol x kg-1 x min-1 in studies I-V, respectively (P < 0.05 for study I vs. basal, P < 0.01 for studies II-V vs. basal, and NS for studies IV and V vs. study III). LOX increased from a basal value of 0.31 +/- 0.04 to 0.38 +/- 0.05, 0.41 +/- 0.02, 0.64 +/- 0.04, 1.11 +/- 0.07, and 1.56 +/- 0.05 micromol x kg-1 x min-1 in studies I-V (all P < 0.01 vs. basal; P < 0.05-0.01 for each study vs. preceding study). Basal NOLD averaged 1.96 +/- 0.2 and did not change significantly in studies I and II (2.03 +/- 0.2 and 2.10 +/- 0.1 micromol x kg-1 x min-1). In contrast, a significant increase in NOLD was observed in studies III, IV, and V (to 2.3 +/- 0.15, 2.74 +/- 0.2, and 3.25 +/- 0.7 micromol x kg-1 x min-1, respectively; all P < 0.01 vs. basal; P < 0.05-0.01 for each study vs. preceding study). The net leucine balance (difference between ELF and NOLD)(-0.31 +/- 0.06 micromol x kg-1 x min-1) became less negative in study I (P < 0.01 vs. basal) and positive during studies II-V when the rise in plasma total amino acid levels was >/= 50% above basal level (P < 0.01 vs. each preceding study). In conclusion, NOLD, ELF, and LOX exhibit a differential responsiveness to acute changes in substrate availability: 1) small increments (25-50%) in plasma amino acid levels inhibit ELF and stimulate LOX but have no effect on NOLD; 2) stimulation of NOLD is observed only with increments in plasma amino acid levels >/= 100% above basal values; and 3) increments in plasma amino acid concentrations > 100% above basal values cause a progressive dose-related increase in LOX and NOLD but do not induce any further inhibition of ELF.

Adult↗
PubMed1996

Neutrophil apoptosis induced by proteolytic enzymes.

In this study, we show that three proteolytic enzymes of different specificity-pronase, chymotrypsin, and trypsin-induced a dramatic stimulation of neutrophil apoptosis as shown by morphologic characteristics, analysis of cell DNA content, and presence of a characteristic "ladder" pattern of DNA fragmentation. The action of either chymotrypsin or trypsin was completely prevented by the serine protease inhibitor aprotinin, indicating that the proteolytic activity of the enzymes accounts for apoptosis induction. Stimulation of neutrophil apoptosis by proteases was observed in culture medium supplemented with either inactivated fetal calf serum (0.1-50%), autologous serum (0.1-50%), bovine serum albumin (0.1%), or in protein-free medium. Other cell types such as human peripheral blood monocytes and lymphocytes, human leukemic cells from THP-1, HL-60 and K562 lines, murine L929 fibroblasts, and unstimulated murine macrophages harvested from the peritoneal cavity were not induced to undergo apoptosis after the treatment with proteases. In an attempt to determine whether neutrophil serine proteases could induce apoptosis as chymotrypsin and trypsin do, the effect of elastase was assessed. A significant increase in the percentage of apoptotic cells was observed in elastase-treated neutrophils. We propose that the selective stimulation of neutrophil apoptosis by proteolytic enzymes may play an important role in the normal resolution of inflammation by limiting the autotoxic potential of the neutrophil.

Animals↗
PubMed1996

Cell proliferation and ploidy of human solid tumours: methodological experience with in vivo bromodeoxyuridine and DNA flow cytometry.

A sequential procedure for single and multiparameter flow cytometry (FCM) that allows detailed cell proliferation and DNA ploidy studies of human solid tumours is reported here. This description includes time collection and storage, tissue disaggregation and staining as well as FCM analysis of samples. The overall feasibility, together with some critical aspects of the DNA/bromodeoxyuridine (BrdU) in vivo assay for cell kinetic studies in human solid tumours, are reported, based on our experience in recent years. We found that the BrdU in vivo method, coupled with bivariate FCM for measurements, is a valuable approach for a 'dynamic' assessment of tumour cell proliferation in the clinical setting. Routine measurements can be achieved providing that well standardised tissue disaggregation and immunolabelling procedures are performed. In different solid tumours, cytokinetic results were satisfactory in 85% of cases as far as the BrdU-labelling index is concerned while 70% were acceptable for DNA synthesis time and tumour potential doubling time. Causes of failure are also considered and discussed. In order to guarantee the finest detection of aneuploidy, routine high resolution single-parameter DNA analysis is suggested. Our experience with further improvements in cell kinetic studies based on the possibility of gating the BrdU/DNA analysis for a subpopulation of interest (i.e. cytokeratin-positive cells in epithelial tumours) is also reported.

Bromodeoxyuridine↗