Comparison between thrombotic risk scores in essential thrombocythemia and survival implications.

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan-Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET-t prognostic score or the current stratification for the thrombotic risk, high-risk patients are always highly represented. This evidence is of note, being the high-risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high-risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow-up of ET despite current recommendations, having a significant impact on morbidity and survival.

Predisposition to vasovagal syncope in subjects with blood/injury phobia.

BACKGROUND: Most subjects with blood/injury phobia experience syncope or presyncope as part of the phobic response. We tested the hypothesis that these subjects have a constitutional autonomic dysregulation that predisposes them to vasovagal syncope during head-up tilt. METHODS AND RESULTS: We studied 11 subjects (9 females, 2 males) who had a history of syncope or presyncope only in response to a blood or injury stimulus and 11 healthy matched controls (10 females, 1 male) without a history of syncope. Blood pressure (BP) and heart rate (HR) were measured during a 15-minute baseline period with subjects in the supine position and then during 45 minutes of head-up tilt to 70 degrees. Measurements at rest did not differ between the blood phobic and control subjects. During tilt, 9 (82%) of the 11 blood phobic subjects experienced presyncope or syncope, leading to termination of the study after 22+/-17 minutes of tilt. Only 1 (9%) of the 11 control subjects experienced presyncope (chi(2)=11.7, P=0.001). Hemodynamic responses to tilt were consistent with a vasovagal mechanism in the blood phobic subjects, with simultaneous decreases in BP and HR during tilt. During tilt, systolic BP fell by 21+/-15 mm Hg (P=0.001), and HR fell by 22+/-25 bpm (P=0.01). By contrast, BP and HR were very stable in the control group. CONCLUSIONS: Subjects with syncope related to blood/injury phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Fainting related to these stimuli may in large part be due to dysfunction in neural circulatory control, which may secondarily lead to the phobia because of repeated syncopal events.

Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea (OSA) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges, each of which may impair endothelial function. We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation, even in the absence of overt cardiovascular disease. METHODS AND RESULTS: We studied 8 patients with OSA (age 44+/-4 years) and 9 obese control subjects (age 48+/-3 years). Patients with OSA were newly diagnosed, never treated for OSA, on no medications, and free of any other known diseases. All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA. Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine (a vasodilator that stimulates endothelial release of nitric oxide), sodium nitroprusside (an exogenous nitric oxide donor), and verapamil (a calcium channel blocker). Conduit-vessel function was also evaluated by ultrasonography. Brachial artery diameter was measured under baseline conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). Patients with OSA had a blunted vasodilation in response to acetylcholine (P:<0.007), but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects. No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects. CONCLUSIONS: Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation. This may be implicated in the pathogenesis of hypertension and heart failure in this condition.

Independent association between plasma leptin levels and heart rate in heart transplant recipients.

BACKGROUND: Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies. The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. METHODS AND RESULTS: We studied 32 male patients (mean age, 56.5+/-9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (r=0.47, P=0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (r=0.73, P<0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (F=2.61, P=0.017). We also observed a strong, independent association between leptin levels and body mass index (F=5.8, P<0.00001). CONCLUSIONS: We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors.

An independent relationship between plasma leptin and heart rate in untreated patients with essential hypertension.

OBJECTIVE: To test the hypothesis that hemodynamic measurements in patients with essential hypertension are related independently to plasma leptin levels. PATIENTS AND METHODS: We measured plasma leptin, insulin, office and ambulatory blood pressure and heart rate in 60 men with untreated mild hypertension. RESULTS: Plasma leptin correlated significantly with body mass index (r = 0.43, P = 0.001), 24 h heart rate (r = 0.35, P = 0.006) and 24 h diastolic blood pressure (r = 0.27, P = 0.04) but not with age (r = 0.03; P = 0.85) or 24 h systolic blood pressure (r = -0.08, P = 0.56). Plasma leptin levels adjusted for body mass index correlated significantly with 24 h heart rate (r = 0.36, P = 0.005) but not with 24 h diastolic blood pressure (r = 0.19, P = 0.15). We divided the patient population into tertiles of body mass index-adjusted plasma leptin levels. Age, plasma insulin, blood pressure, smoking status and physical activity habits were similar across the adjusted leptin tertiles. Patients from the third tertile of adjusted plasma leptin distribution (those with leptin levels higher than would be expected on the basis of body mass index) had significantly faster ambulatory heart rates than subjects from both the first and the second tertiles. The difference in heart rate across the three tertiles was most pronounced for the night-time values. CONCLUSIONS: In patients with essential hypertension, heart rate is faster in those patients with higher plasma leptin levels. This relationship is independent of age, body mass index, insulin levels, blood pressure level, smoking status and physical activity.

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): a multicentre phase II clinical trial.

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37-73) and a median ECOG performance status of 1 (range 0-2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m(2) diluted in 250 cc(3) of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m(2) on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3-7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22-52%) had a partial response for an overall response rate of 40% (95% CL 26-56%). Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3-4 neutropenia was recorded in 22% of cases, grade 1-3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.

Prevalence and clinical correlates of microalbuminuria in stage I hypertension. Results from the Hypertension and Ambulatory Recording Venetia Study (HARVEST Study).

The objective of the present study was to examine the association between albumin excretion rate (AER) and office and ambulatory blood pressures (BP), and other recognized cardiovascular risk factors in stage I hypertension. The study was carried out in 870 never-treated 18- to 45-year-old hypertensives (628 men, 242 women). Office and ambulatory BP, 24-h urinary collection for AER assessment, and echocardiographic left ventricular mass (n = 587) were obtained. AER was similar in men and women (12.3 v 12.5 mg/24 h) and was unrelated to age and body mass index. In 85.2% of the subjects, AER was < 16 mg/24 h, in 8.3% it was between 16 and 29 mg/24 h (borderline microalbuminuria), and in 6.1% it was >or= 30 mg/24 h (overt microalbuminuria). Office systolic BP was not different in the three groups, whereas 24-h systolic BP was higher in the subjects with microalbuminuria than in those with normal AER (P < .0001) and was similar in the two microalbuminuric groups. Office and 24-h diastolic BPs were higher in the subjects with overt microalbuminuria than in those with normal AER. Left ventricular mass was correlated to systolic (P < .0001) and diastolic (P = .01) 24-h BP, but was unrelated to AER. Family history for hypertension, smoking, coffee and alcohol intake, and physical activity habits did not influence AER. In a logistic regression analysis, 24-h systolic BP emerged as the only determinant of microalbuminuria (P < .0001). In conclusion, these results indicate that borderline levels of microalbuminuria may also be clinically relevant in stage I hypertension. Overweight and lifestyle factors do not appear to influence AER in these patients. Finally, the lack of correlation between AER and left ventricular mass suggests that renal and cardiac involvement do not occur in a parallel fashion in the initial phase of hypertension.

Rhythms, rhymes, and reasons--spectral oscillations in neural cardiovascular control.

Cardiovascular neural regulation is an integrated response to a continuous interaction of inhibitory and excitatory stimuli. Neural control of the circulation appears to be coded simultaneously in different modalities as amplitude (strength of signal or tonic activity) and frequency (oscillatory or phasic activity). Changes in tonic activity appear to be accompanied by tightly linked modulations in oscillatory characteristics. This is true within a narrow range of physiologic conditions, and the relationship is eliminated in extreme cardiovascular pathophysiology. Nevertheless, the oscillatory patterns in cardiovascular neural control appear to be widespread so that low and high frequency oscillatory patterns are evident even in sympathetic traffic to skin (Cogliati et al., 2000). Thus, it is likely that there is a functional significance to these oscillations. Recent data from Nafz et al. (1999) suggest that the presence of LF oscillatory characteristics in renal perfusion may attenuate renin-angiotensin activation during renal hypotension. These findings may have direct relevance to poorer outcomes observed in heart failure patients in whom an absence of LF oscillatory power was observed in RR interval and sympathetic traffic (Van de Borne et al., 1997a).

Sleep apnea and hypertension.

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing and frequently coexists with obesity. Almost 15 million Americans are affected by this disorder. This prevalence is likely increasing, given the current epidemic of obesity. Recent data confirm an association between sleep apnea and several cardiovascular disease conditions, suggesting that OSA may be a new risk factor for coronary artery disease, heart failure, heart rhythm disturbances and hypertension, independent of body mass index. In this review, the authors focus on the nature of the association between OSA and hypertension, the evidence suggesting a causal interaction, and discuss the potential pathophysiologic mechanisms responsible. These mechanisms include activation of the sympathetic and renin-angiotensin-aldosterone systems (RAAS), oxidative stress, and systemic and vascular inflammation, all of which could link OSA to a sustained increase in blood pressure. The authors also review potential therapeutic strategies for the hypertensive patient with OSA.

[Monoclonal antibody assessment of lymphocyte subpopulations in rheumatoid arthritis in adult patients in relation to stage and treatment]. / Valutazione con anticorpi monoclonali delle sub-popolazioni linfocitarie nell'artrite reumatoide dell'adulto, in rapporto allo stadio ed al trattamento.

Twenty patients with various stages of RA were examined. They included: 1) 7 cases in Steinbroker stage 1 (onset); 2) 13 cases in Steinbroker stage 2-3 (chronic). The group was divided into 16 treated and 4 untreated cases. Monoclonal antibodies were used to assay T3, T4, T8 and T4/T8 ratio and the results were compared with those in a control group. The results showed a T8 deficit and a consequent change in the T4/T8 ratio in untreated subjects with "onset" RA. The immune situation of the chronic and treated cases was very similar to that in the control group probably as a result of treatment.

[Use of immunoglobulins in AIDS]. / Uso delle immunoglobuline in corso di AIDS.

Fourteen AIDS patients with constitutional symptoms without a known etiology were treated with intravenous immunoglobulins (IVIG). The dosage regimen was 300 mg/kg per day three times weekly for two weeks followed by 300 mg/kg per day once weekly for ten weeks. All patients improved clinically after treatment with IVIG. The reason for the clinical improvement in our cases is as yet unclear, but it is possible that immunoglobulins have had a therapeutic effect on the underlying immunologic disturbance.

[High-dose immunoglobulins in immune thrombocytopenic purpura]. / Immunoglobuline ad alte dosi nella porpora trombocitopenica immune.

Twenty-four patients with immune thrombocytopenic purpura (ITP) were treated with high doses of intravenous immunoglobulin (Ig). Increase in platelets was observed in all the patients. The maximum value was reached between the seventh and the twelfth day of treatment. The mean number of platelets was 18 x 10(9)/l before the treatment and 150 x 10(9)/l after the treatment. The effect was transient; in fact, a fall in the platelets was observed after 18 days of treatment. Our study confirms that high doses Ig is an effective treatment of ITP, but the high cost and the temporary effect limit its use only in those cases in which other treatments are ineffective or contraindicated.

Impaired left ventricular filling in hypertensive left ventricular hypertrophy as a marker of the presence of an arrhythmogenic substrate.

OBJECTIVE: To assess the prevalence of ventricular late potentials and ventricular tachycardia in hypertensive subjects with left ventricular hypertrophy and to study their relation to clinical characteristics. SETTING: Teaching and general hospital in Padua. METHODS: 107 hypertensive subjects with echocardiographic signs of left ventricular hypertrophy were studied with signal averaged electrocardiography and 24 hour Holter monitoring. Signal averaged electrocardiogram analysis was performed with high pass filters of 25 Hz, 40 Hz, and 80 Hz. Ventricular late potentials were considered to be present if at least two determinants of the signal averaged electrocardiogram were abnormal in one of the three filters. 70 normotensive subjects served as age matched controls. RESULTS: 25% (27) of the hypertensive subjects and 6% (four) of the controls showed late potentials on signal averaged electrocardiography (P < 0.0001). The hypertensive subjects with late potentials had a higher prevalence of ventricular tachycardia (33%, 9/27) than those without late potentials (13%, 10/80; P = 0.035). Twenty nine per cent (31/107) of the hypertensive subjects had an inversion of the early to atrial filling velocity (E/A ratio < 1) on Doppler analysis of transmitral flow. Within this group the percentage of subjects with late potentials (55%, 17/31) and ventricular tachycardia (42%, 13/31) was much greater than that within the group of subjects without an inverted E/A ratio (13%, 10/76 (P < 0.0001) and 12%, 9/76 (P = 0.001) respectively). In a multivariate analysis only the E/A ratio was related to the presence or absence of either late potentials (P = 0.0001) or ventricular tachycardia (P = 0.0008). Both late potentials and ventricular tachycardia were unrelated to left ventricular mass, geometry, and systolic performance. CONCLUSIONS: A relation was found between the occurrence of ventricular tachycardia and the presence of late potentials in hypertensive subjects with left ventricular hypertrophy. Impaired left ventricular filling was the main marker for the arrhythmogenic substrate present in this disease.

Relation of 24-hour ambulatory blood pressure and short-term blood pressure variability to seasonal changes in environmental temperature in stage I hypertensive subjects. Results of the Harvest Trial.

We investigated the seasonal changes in blood pressure (BP) and in short-term BP variability determined using ambulatory blood pressure monitoring (ABPM). 1000 white subjects, who took part in the multicenter HARVEST study, underwent ABPM with the A&D TM-2420 or the Spacelabs 90207. Standard deviation of the mean daytime and nighttime BP was taken as an index of short-term BP variability (v). Maximal outdoor temperature (Tmax) during each ABPM was obtained from local Meteorological Centers. Subjects were divided according to season and to quartiles of Tmax. A subgroup of 46 persons who repeated ABPM in Winter and Summer was also studied. We observed evident seasonal differences in office and ambulatory systolic BP (SBP) with a peak during Winter. Diastolic BP (DBP) and heart rate did not vary throughout the four seasons. Office SBP (p < 0.01), 24-hour (p < 0.002), daytime SBP (p < 0.0001), both daytime SBPv (p < 0.0001), DBPv (p < 0.02), and nighttime SBPv (p < 0.05), DBPv (p < 0.02) as well as norepinephrine (p < 0.005) were significantly higher during Winter than Summer. Similar differences were observed in subjects grouped in quartiles of Tmax. In the subgroup daytime but not nighttime SBP was higher in the cold season. Average 24-hour SBP (p < 0.05), daytime SBP (p < 0.02), daytime SBPv (p < 0.001) and DBPv (p < 0.05) and norepinephrine (p < 0.0001) were significantly negatively correlated with Tmax in the whole population. BP is higher and subjected to wider oscillations during the cold season in patients with mild hypertension probably due to sympathetic activation. The assessment of a hypertensive subject may give different results according to the season.

[Relations between ventricular late potentials and ventricular arrhythmias in mitral valve prolapse]. / Relazione tra potenziali tardivi ventricolari e aritmie ventricolari nel prolasso valvolare mitralico.

BACKGROUND: The aim of the present study was to assess the prevalence and the clinical significance of ventricular late potentials in mitral valve prolapse. METHODS: Two hundred subjects (126 women and 74 men) with mitral valve prolapse, and a mean age of 37 +/- 17 years, were studied. Fifty eight per cent of them exhibited signs of mitral regurgitation at Doppler analysis of mitral flow. A 24-hour Holter recording and a signal-averaged electrocardiogram were performed in all the patients. Late potentials were considered present if the filtered QRS complex was > 110 ms and the root-mean-square amplitude in the last 40 ms of the filtered QRS was < 25 microV after 25 Hz filtering and respectively > 114 ms and < 20 microV after 40 Hz filtering. The duration of low-amplitude signals < 40 mV had to be > 38 ms. RESULTS: Ventricular late potentials were detected in 45 patients (22.5%) and were unrelated to subjects age, sex and electrocardiographic ST-T changes. Fourty one per cent of the subjects exhibited lown class > or = 3 ventricular extrasystoles at Holter ECG monitoring, while the remaining subjects (59%) had Lown classes < 3 ventricular arrhythmias. Complex ventricular arrhythmias were more common in the subjects who exhibited late potentials (55.5%) than in the remaining population (36.7%) (p < 0.03). A higher frequency of late potentials was found in the patients with mitral regurgitation (34.7%) than in those without (5.8%) (p < 0.0001). In the 55 subjects who manifested mitral regurgitation and complex ventricular arrhythmias, the prevalence of late potentials was 43.6%, while in the 61 without complex arrhythmias the prevalence was 26.6% (p = 0.05). CONCLUSIONS: In subjects with mitral valve prolapse the signal-averaged electrocardiogram allows to identify a subgroup of patients with more serious ventricular arrhythmias. Mitral regurgitation seems to be the main determinant of the arrhythmogenic substrate present in these patients.

HIV infection: oral lesions, CD4+ cell count and viral load in an Italian study population.

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.

[The relationship between overweight, life style and casual and 24-hour pressures in a population of male subjects with mild hypertension. The results of the HARVEST study]. / Relazione tra sovrappeso, abitudini di vita e pressione casuale e delle 24 ore in una popolazione di soggetti di sesso maschile con ipertensione lieve. Risultati dello studio HARVEST.

AIM OF THE STUDY: To evaluate the relationship of coffee use, smoking, physical inactivity, alcohol intake and overweight with casual and ambulatory blood pressure in a large population of borderline to mild hypertensive subjects. METHODS: Six hundred and thirty men with a mean (+/- SE) age of 33 +/- 0.4 years (range = 18-45 years) and a mean office blood pressure of 146 +/- 0.4/94 +/- 0.2 mm Hg, participating in the multicentre HARVEST study, were divided into three categories according to: coffee consumption (0 cups, 1-3 cups, > 3 cups/day), number of cigarettes smoked per day (0, 1-10, 11-20), degree of physical activity (no activity, regular training, competitive activity), alcohol intake (no alcohol, < 50 g, > or = 50 g/day) and body mass index (tertiles). All patients underwent non invasive ambulatory blood pressure monitoring with either the A&D TM-2420 model 7 or the Spacelabs 90207 monitor. Moreover, 24-hour urine collection was made for epinephrine and norepinephrine assessment (n = 611). RESULTS: Twenty-four-hour systolic blood pressure was higher in the coffee drinkers than the nondrinkers (+2.6 mm Hg in the moderate drinkers). Instead, 24-hour diastolic blood pressure was mainly influenced by overweight (3.2 mm Hg difference between the low and high BMI tertiles) and physical inactivity (3.2 mm Hg difference between the sedentary men and the athletes). Generally, the association of the above factors was stronger with ambulatory than with office blood pressure, whereas alcohol intake was only related to office diastolic blood pressure. However, in a multivariate regression analysis alcohol use did not show an independent effect on either office or ambulatory blood pressure. Smoking showed a different effect on office and ambulatory blood pressure. In fact, office blood pressure was higher in the nonsmokers, while 24-hour blood pressure was higher in the smokers. Smoking, coffee and physical inactivity were associated with sympathetic overactivity, as documented by increased urinary catecholamines output. CONCLUSIONS: The results of the present study indicate that overweight and behavioural factors affect 24-hour blood pressure to a larger extent than office blood pressure does. This is likely to be due to their effect on the sympathetic nervous system activity, which would enhance the blood pressure response to daily life stressors.

Hodgkin's disease presenting below the diaphragm. The experience of the Gruppo Italiano Studio Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Infradiaphragmatic Hodgkin's disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of this condition. METHODS: A series of 282 patients with CS I-II Hodgkin's disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups. RESULTS: The BDHD group was older (p < 0.0002), had a higher frequency of males (p < 0.08) and a different histological subtype group distribution (p < 0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p < 0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with ADHD. BDHD patients with intra-abdominal disease alone had worse prognostic factors and OS (p = 0.12) than patients with inguinal-femoral nodes. INTERPRETATION AND CONCLUSIONS: Although BDHD patients present distinct features, they have the same OS and relapse-free survival rate as age-adjusted ADHD patients. According to our experience patients with stage I peripheral BDHD respond well to radiotherapy-based regimens. Those with stage II and or intra-abdominal disease are more challenging; chemotherapy or a combined therapy seem to be more suitable approaches for these patients.

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.