Long-term outcomes of a pilot CT screening for lung cancer.

BACKGROUND: Low-dose computed tomography (CT) screening can detect early stage lung cancer in high-risk populations. However, no data on repeated annual screening over more than 5 years are available, and the impact of screening on lung cancer mortality is controversial. METHODS: We analysed outcomes in high-risk asymptomatic volunteers (smokers and former smokers, >50 years) enrolled in a pilot study over 1 year from June 2000, who received annual low-dose CT for 7 years. Cumulative lung cancer incidence and survival were represented by Kaplan-Meier curves. Standardized incidence and mortality ratios were used to estimate risks relative to the general Italian and US population. RESULTS: Compliance was 86% at the end of the seventh year in 1035 recruited volunteers (71% men, mean age 58 years). Lung cancer was diagnosed in 54 (5.3%); radical surgery was possible in 48/54 (87%); 39/54 (72%) had stage I disease. Five-year survival was 63% overall, 89% for stage I cases. During 6308 person-years of observation, 47 participants had died versus 75 expected in the Italian general population standardised for age and sex. Fourteen lung cancer deaths were registered versus 27 expected in a standardised US smoker population. CONCLUSIONS: Seventy percent of screening-diagnosed patients had stage I disease, and the survival of screen-detected cancer patients was high. Lung cancer mortality was favourable compared to age- and sex-matched population of US smokers, suggesting that mortality can be lowered by screening, although larger trials with longer follow-up are necessary to confirm these findings.

Synchronous pleuro - renal solitary fibrous tumors: a new clinical-pathological finding.

Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal neoplasms usually originating from the visceral pleura, but sometimes found in other sites like the orbit, dura, paranasal sinus, upper respiratory tract, thyroid, sublingual gland, lung, periosteum, cauda equina, ovary, scrotum and testicular tunica vaginalis. Solitary fibrous tumor of the kidney is extremely rare with fewer than 15 reported cases in modern English literature. To the best of our knowledge, this report describes the first known case of synchronous SFTP in the left parietal pleura and left kidney. The SFTP of the pleura, widely compressing and displacing the left lower lung lobe, was resected via left thoracotomy, whereas the renal SFTP, diagnosed by echo-guided histological biopsy, was closely monitored by computed tomography scan and ultrasound. After a one-year follow-up no recurrence was detected in the left hemithorax and the renal lesion remained stable.

Vascular catheter mimicking persistent left superior vena cava.

We report the case of a 42-year-old woman with a double vascular catheter mimicking a false persistent left superior vena cava on a chest X-ray. Physicians should be aware of the correct course of these catheters in order to avoid serious clinical consequences.

Pneumocephalus after Pancoast's tumor surgery: to be or not to be conservative?

We report a case of a 62-year-old man affected by Pancoast's tumor who developed pneumocephalus 17 days after right upper lobectomy with en bloc resection of the first three ribs and C8-D1 branches of the brachial plexus. The patient complained of aphasia, disorientation and sphincterial release. A chest and brain-CT scan showed a right apical pneumothorax associated with a massive pneumocephalus of the ventricles and of the subarachnoidal spaces. A pneumoperitoneum was also seen. The patient was treated using pleural drainages, Trendelenburg's position and antibiotic therapy. Clinical and radiological remission was achieved after 12 days of additional hospital stay.

A safe and effective method for an immediate bronchopleural fistula repair.

Bronchopleural fistula (BPF) is a well recognized and potentially fatal complication of major thoracic surgery and several strategies regarding its prevention and subsequent management have been described. An immediate BPF occurring intraoperatively after bronchial closure is a rare event and is usually treated by bronchial stump reamputation and/or hand-suture reinforcement by mattress suture, or myoplasty. We report a simple and successful technique, using azygous vein flaps, to repair an intraoperative BPF associated to a small bronchial dehiscence occurred after a right pneumonectomy in a 70-year-old diabetic man receiving induction chemotherapy treatment.

[Technique, results and impact of induction chemotherapy in sleeve lobectomy for lung cancer]. / Tecnica, risultati e ruolo della chemioterapia di induzione nella lobectomia con resezione/anastomosi bronchiale (sleeve).

AIM: The aim of this study was to evaluate the safety of continuous nonabsorbable (3/0 polypropylene) sutures for sleeve lobectomy, and the influence of induction chemotherapy on postoperative outcome in patients with lung malignancies. METHODS: A review of a prospective database of a single surgeon identified 41 consecutive patients who underwent sleeve lobectomy from May 1998 to July 2003. Bronchial reconstruction was done placing two 3/0 polypropylene sutures at the far side of the cartilaginous wall and subsequently fixed. Afterwards, two running sutures were performed in order to obtain a telescopic anastomosis. RESULTS: Twenty-four patients (59%) underwent induction chemotherapy. There were 31 right upper, 3 left lower ''reverse'', and 7 left upper sleeve lobectomies with radical lymph node dissection. Eight patients underwent reconstruction of the pulmonary artery. There were 34 non-small cell lung cancers, 3 limited small cell lung cancers, 1 neuroendocrine large cell carcinoma, and 3 bronchial carcinoid tumors. N2, N1, and N0 diseases were found in 13, 12 and 16 patients, respectively. Post-operative morbidity and mortality were 14.5% (n=6) and 4.8% (n=2) (1 patient, 4%, after induction chemotherapy). The rate of postoperative anastomotic complications was 2.4% (n=1). Late bronchial stenosis developed in 3 cases, but all were successfully medically treated. Twenty-nine patients are still alive, 27 without evidence of disease. The overall 2-year probability of survival (Kaplan-Meier) was 59%. Induction chemotherapy did not influence postoperative morbidity/mortality (chi2 test: P=0.64/P=0.56). CONCLUSIONS: Continuous nonabsorbable suture for sleeve lobectomy is quick and technical easy to perform, with low postoperative morbidity/mortality; induction chemotherapy does not influence postoperative outcome in these patients.

Extended redo sleeve resection for postoperative dehiscence after right upper bronchoplasty.

Complete anastomotic dehiscence after sleeve resection is a dramatic and often fatal event requiring an extremely aggressive and risky treatment; completion pneumonectomy represents the sole effective therapeutic option to rescue the patient, but postoperative mortality after this procedure is high. We report a case successfully treated by extended redo carinal sleeve resection after full bronchial dehiscence. This option should be taken into account in such a complication, mainly in patient with compromised respiratory function.

Management of true splenic artery aneurysms. Two case reports and review of the literature.

Few series of splenic artery aneurysms (SAA) have been reported, but today asymptomatic SAA are detected with increasing frequency. Their importance lies from their potentially fatal consequences as life-threatening hemorrhage. SAA management still remains controversial as reported in this review. Our 2 patients treated with resection of the aneurysms, both located in the middle third of the splenic artery. Some authors demonstrated that when splenic artery has been ligated (or embolized) and the patients remain anatomically splenic, they may not retain any splenic function. Laparoscopic SAA ligation repair appears to be optimal and useful for aneurysms protruding from the pancreas and it is gaining interest because clinical recovery is rapid with a poor morbidity and economic and cosmetic advantages. Transcatheter embolization too offers a temporary control in urgency to stop hemorrhage and go back at later date to make much better elective operation. Endovascular interventions as percutaneous embolization has recently gained popularity: it offers a safe alternative or adjunctive therapy to traditional surgery. We hope in the future instrumentation will likely improve so that this procedure can be done percutaneously by development of prosthetic devices in the 21th century.

Stair-climbing test to evaluate maximum aerobic capacity early after lung resection.

BACKGROUND: The aim of this study was to investigate the extent of reduction in maximum oxygen consumption in the early postoperative period after lung resection for lung carcinoma. METHODS: A total of 115 patients who underwent lung resection (95 lobectomies, 20 pneumonectomies) performed a maximal stair-climbing test the day before operation and the day of discharge from the hospital (8 +/- 3.3 days after the operation). RESULTS: The postoperative test showed a 15% reduction in maximum oxygen consumption (VO2max) with respect to the preoperative test (Student's t test, p < 0.0001). This reduction was greater after pneumonectomy (21.4%) than after lobectomy (14%) (Student's t test, p < 0.05). A multiple regression analysis showed that the only significant independent predictors of both preoperative and postoperative VO2max were the age of the patient and the level of arterial oxygen content. CONCLUSIONS: The early postoperative reduction in VO2max was greater after pneumonectomy than after lobectomy and the exercise performance was significantly influenced by the level of arterial oxygen content both before and early after the operation.

Early and late (ten years) experience with circular stapler hemorrhoidectomy.

PURPOSE: We present a retrospective clinical study concerning the preliminary experience with the circular stapler in the treatment of hemorrhoids. Early results, complications, and long-term follow-up are revisited. METHODS: Fifty-six consecutive patients with second-, third-, and fourth-degree hemorrhoids were included in the study. Data about operation, early postoperative results, and follow-up at one, two, and four weeks were collected. Patients were also contacted by phone after a long-term follow-up (mean, 33 (range, 5-120) months). RESULTS: Every operation attempted was successfully terminated. The length of the operation was less than 15 minutes. No major bleeding or anastomotic disruption occurred. Six patients (13 percent) who underwent spinal or epidural anesthesia had urinary retention. One patient (1.7 percent) had minor bleeding, and four patients (7.1 percent) experienced transient edema of the anastomotic ring after the operation. None needed further treatments. The mean analgesic requirement was 1.4 (range, zero to eight) ketorolac 30-mg injections; 23 patients (41 percent) received no analgesics, and seven patients (12 percent) required a single extra dose of opiates (10 mg morphine cloridrate). Length of hospital stay was between 0 and 11 (mean, 2.7) days, but 20 patients (35 percent) received an additional operation for coexisting surgical disease. At one week, almost all patients experienced little pain at digital inspection and little bleeding after defecations. No anastomotic leakage, wound infection, or healing delay was found. Three patients (5.3 percent) experienced wound edema and pain during defecation. Two weeks later, one patient (1.7 percent) suffered from painful defecation and ten patients (17 percent) reported minor bleeding, but all returned to normal activities. No pain during defecation, bleeding, stenosis, soiling, incontinence, or other anal symptoms were found at one month after the operation, and all patients were well. All patients were contacted by phone 5 to 120 (mean, 33) months later, and all were pleased with the results of this procedure. There were no symptomatic recurrences. DISCUSSION: Our study confirms the feasibility of circular stapler hemorrhoidectomy in the treatment of hemorrhoids. Complications and postoperative pain were minimal. There were no recurrences during long-term follow-up. CONCLUSION: Mechanical hemorrhoidectomy is a promising new option in the treatment of all patients eligible for a surgical approach.

Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients.

The factors determining the outcome of immunotherapy in metastatic renal cell carcinoma (RCC) patients remain elusive. Macrophages from normal donors that phagocytose apoptotic cells secrete the immunosuppressive cytokine IL-10 in vitro. Conversely, IL-10 genetic deletion enhances the immunogenicity of apoptotic tumor cells in vivo. Elevated pre-treatment levels of IL-10 are associated with an unfavorable outcome of RCC. We examined whether the ability to release IL-10 by macrophages from RCC patients that phagocytosed apoptotic cells correlated with the outcome of immunotherapy. To this aim, we derived macrophages from 30 patients with metastatic RCC and from 21 healthy subjects (11 sex- and age-matched healthy controls and 10 younger donors). Patients either had a clinical response after immunotherapy, with a median survival after treatment of more than 18 months (n = 16), or were beginning immunotherapy after diagnosis of metastatic disease (n = 14). Macrophages from responding patients challenged with apoptotic cells released significantly less IL-10 than controls (p = 0.0075) and recently diagnosed patients (p = 0.0198), as ascertained by a 2-sided Student's t-test. This was not because macrophages from responding patients lost the ability to secrete IL-10, because antibody opsonization of apoptotic cells rescued IL-10 secretion. In contrast, macrophages from all groups of donors released similar amounts of TNF-alpha. The failure in IL-10 secretion by engulfing macrophages of responding subjects may exalt the immunogenicity of dying tumor cells, contributing to the success of immunotherapy.

Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12.

Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 microg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a high-efficiency limiting dilution analysis technique within a few days after rHuIL-12 injection. A similar burst in peripheral CTLp frequency was observed even when looking at response to a single tumor-derived peptide, as documented by an increase in Melan-A/Mart-1(27-35)-specific CTLp in two HLA-A*0201+ patients by limiting dilution analysis and by staining peripheral blood lymphocytes (PBLs) with HLA-A*0201-melanoma antigen-A/melanoma antigen recognized by T cells (Melan-A/Mart)-1 tetrameric complexes. The CTLp burst was associated, in PBLs, with enhanced expression of T-cell adhesion/homing receptors CD11a/CD18, CD49d, CD44, and with increased proportion of cutaneous lymphocyte antigen (CLA)-positive T cells. This was matched by a marked increase, in serum, of soluble forms of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecules (VCAM)-1 and intercellular adhesion molecules (ICAM)-1. Infiltration of neoplastic tissue by CDS+ T cells with a memory and cytolytic phenotype was found by immunohistochemistry in eight of eight posttreatment metastatic lesions but not in five of five pretreatment metastatic lesions from three patients. Increased tumor necrosis and/or fibrosis were also found in several posttherapy lesions of two of three patients in comparison with pretherapy metastases. These results provide the first evidence that rHuIL-12 can boost the frequency of circulating antitumor CTLp in tumor patients, enhances expression of ligand receptor pairs contributing to the lymphocyte function-associated antigen-1/ICAM-1, very late antigen-4/VCAM-1, and CLA/E-selectin adhesion pathways, and promotes infiltration of neoplastic lesions by CD8+ memory T cells in a clinical setting.

Bizarre leiomyoma of the epididymis. A case report.

A case of epididymal leiomyoma with bizarre nuclei is described. A 48-year-old man presented with a painless scrotal mass raising the suspicion of a testicular neoplasm. A seven-year follow-up revealed no evidence of local recurrence or distant metastasis. To personal knowledge, this is the first reported case of bizarre leiomyoma of the epididymis.

[On the subject of pancreatic ductal carcinoma]. / In tema di carcinoma duttale pancreatico.

Pancreatic cancer is a dismal disease. The 5-year overall survival ranges from 1% to 5%. Surgery is the only curative treatment available for this cancer, but it is indicated only in selected patients with a less than 4 cm tumor. In these patients, survival rate is about 30%. We have considered several aspects: the very difficult early diagnosis, the correct diagnostic flow chart, actual surgical procedures and new trends in biologic and genetic research. It is likely that better results can be achieved by defining an "early pancreatic cancer" and establishing how to detect it. This could be the wrigth one way is to significantly improve the survival of these patients.

Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma.

The aim of this study was to evaluate the safety profile of s.c. administered recombinant human interleukin 12 (rHuIL-12). Pharmacokinetics and pharmacodynamics of rHuIL-12 and any evidence of antitumor effect were also considered. Ten pretreated patients with progressive metastatic melanoma were enrolled in this pilot study. Patients received a fixed dose of rHuIL-12 (0.5 microgram/kg) for two identical 28-day cycles, with injections given on days 1, 8, and 15 of each cycle. In case of any evidence of response or disease stabilization, the treatment was continued for two further 28-day cycles. Toxicity mainly consisted of a flu-like syndrome. Transient increases in transaminasemia (6 of 10 patients) and triglyceridemia (8 of 10 patients) were observed. Peak serum IL-12 levels were reached 8-12 h after the first injection in all patients; no serum IL-12 was detectable in 6 of 9 evaluable patients after the last injection of the second cycle. No antibody response to rHuIL-12 could be detected in any of the patients. A marked, transient reduction in circulating CD8+ and CD16+ lymphocytes and neutrophils was observed after the first administration and high levels of serum IFN-gamma and IL-10 were detected in all patients within 24-48 h. Tumor shrinkage, not reaching partial or complete remission, involved the regression of s.c. nodules (2 of 3 patients), superficial adenopathies (1 of 3 patients), and hepatic metastases (1 of 3 patients); regressions were detected after the first cycle of treatment and were maintained in spite of progression at different sites. s.c. rHuIL-12 treatment was well tolerated and had marked effects on immune parameters and potential antitumor activity.

TCR expression and clonality analysis in peripheral blood and lymph nodes of HIV-infected patients.

We compared the T cell receptor (TCR) V beta gene family repertoire in peripheral blood mononuclear cells (PBMC) and lymph node (LN) cells from 7 human immunodeficiency virus (HIV)-infected patients and 3 seronegative healthy controls. Virtually all the V beta family specificities were represented in patient PBMC and LN cells, and mean values for each specificity were comparable to figures in seronegative controls. In 4 patients, however, some V beta gene segment transcripts were overrepresented in the LN compartment, compared to the peripheral blood counterpart. To ascertain whether this phenomenon was due to polyclonal or oligoclonal expansion of T cells bearing the relevant V beta gene product, we sequenced the entire CDR3 region of a panel of 238 PCR clones corresponding to the V beta transcripts expanded in LN; as control, the same regions were cloned and sequenced in patient's PBMC, and in PBMC and LN cells from seronegative individuals. This analysis disclosed preferential usage of J beta 2 genes in PBMC and LN cells from both seropositive patients and controls, regardless of the V beta gene segment considered, thus indicating that this skewness in the V beta-J beta repertoire could be a consistent feature of at least a part of the V beta repertoire in different lymphoid compartments, regardless of the pathologic conditions. In addition, in LN from HIV seropositive patients we found the presence of recurrent TCR rearrangements, accounting for 8-23% of the generated clones, in each of the 4 V beta specificities analyzed; recurrent sequences were not found in PBMC from patients nor in PBMC and LN cells from seronegative controls. These findings suggest that antigen-driven oligoclonal T cell expansions may occur in vivo in lymphoid organs of HIV seropositive patients.

B and T cell function parameters during zidovudine treatment of human immunodeficiency virus-infected patients.

The aim of this study was to assess the effects of zidovudine on B cell dysregulation in human immunodeficiency virus (HIV)-infected patients and the phenomenon of gp 120/anti-gp 120 antibody complex adhesion to CD4+ cells. Compared with pretherapy figures, zidovudine treatment was not associated with a change in spontaneous in vitro synthesis of anti-HIV antibodies but was related to restoration of lymphocyte ability to produce Epstein-Barr virus-specific antibodies in 43% of previously unresponsive patients. After 30 days of therapy, the percentage of circulating CD4+/IgG+ lymphocytes decreased; the number of available CD4 receptors per cell increased, and antibodies to gp 120, evident in CD4+ cell eluates from most untreated patients, were no longer detectable. These results indicate that zidovudine partly restores in vitro humoral responsiveness but does not substantially influence the overall activation of the B cell compartment. The findings also suggest that zidovudine may down-regulate some immunopathologic phenomena that amplify direct viral damage.

Impaired left ventricular filling rate induced by treatment with recombinant interleukin 2 for advanced cancer.

BACKGROUND: Immunotherapy with recombinant interleukin 2 (rIL 2) has been extensively used to treat cancer but its use has been hampered by serious side effects including severe hypotension, arrhythmias, and myocardial infarction. OBJECTIVE: To assess the effects of rIL 2 on human left ventricular function. METHODS: Left ventricular (LV) function was monitored in 22 patients (9 women, 13 men) (mean (SD) age 53 (10) years) undergoing a 120 h continuous intravenous infusion of rIL 2 (18 x 10(6) IU/m2/day) for melanoma (4), renal cell (16), ovarian (1), and colon cancer (1). Radionuclide ventriculography was performed before and 1 h after the end of treatment. Ejection fraction (EF), peak emptying rate (PER), peak filling rate (PFR), and regional left ventricular wall motion were analysed. Heart rate (HR), central venous pressure (CVP), systolic (SBP) and diastolic blood pressures (DBP), the electrocardiogram, and myocardial enzyme concentrations were monitored throughout the study. RESULTS: All variables (mean (SD)) were normal before rIL 2 was given. After rIL 2 administration HR increased significantly from 84 (11) to 125 (18) beats/min (p < 0.0001), SBP fell from 128 (11) to 100 (9) mmHg (p < 0.001) and DBP from 76 (9) to 65 (7) mmHg (p < 0.0001). CVP decreased from 3.70 (3.2) to 1.30 (0.45) cm H2O (p < 0.001). EF (65 (7) to 64 (8%) and PER (3.56 (0.60) to 3.86 (0.83) EDV/s) did not change significantly. PFR decreased significantly at the end of the rIL 2 infusion from 2.68 (0.46) to 2.37 (0.43) EDV/s (p < 0.01). Left ventricular segmental hypokinesia developed in 6 patients. Myocardial enzyme concentrations remained normal throughout the study. CONCLUSIONS: The results of this study confirmed that rIL 2 produces important haemodynamic changes, predominantly related to decreased systemic resistance. However, the observed reduction in PFR in most patients suggested that rIL 2 might exert its action at the level of the heart muscle itself. The localised systolic dysfunction in some patients suggested that rIL 2 might also adversely affect myocardial perfusion.

Treatment of advanced renal cell cancer with sequential intravenous recombinant interleukin-2 and subcutaneous alpha-interferon.

Starting from in vitro studies suggesting synergistic antitumour activity against renal cell cancer (RCC) of recombinant interleukin-2 (rIL-2) and alpha-interferon (IFN), a phase II trial was initiated to test the clinical activity of this combination. The two cytokines were administered sequentially, with the aim of reducing the risk of additive toxicity and enhancing the immunological reaction against the tumour. The original treatment schedule consisted of rIL-2 18 x 10(6) U/m2/day by continuous intravenous infusion for 120 h days 1-5, and alpha-IFN 2b, at a flat dose of 9 x 10(6) U by subcutaneous or intramuscular injection thrice in a week, from day 8 to 28. Treatment was planned to be continued for six or more 28-day cycles, depending on clinical response. 12 patients were treated according to this schedule; as some cardiovascular toxicity was experienced in this set of patients, 11 further patients were treated with half-dose rIL-2 (i.e. 9 x 10(6) U/m2/day). 17 out of 23 enrolled patients completed at least one cycle of treatment and were evaluated for response. We observed six major responses [one complete response (CR) + five partial responses (PR)] for an objective response rate of 35% [95% confidence interval (CI) 17-59%]. 5 additional patients achieved stabilisation of disease; one of them reached CR after surgical extirpation of a lung mass. Sites of response included lung, nodes and bone. Duration of response is 12+ months for CR; 17, 16, 12+, 9 and 9 months for PRs. Median survival is 16 months. Response was not significantly different between full-dose and half-dose rIL-2. Considering stable disease (SD) as responses, there seemed to be a higher chance of response for patients with smaller tumour burden (P = 0.032). The toxicity of rIL-2 treatment, mainly cardiovascular, was substantial; 9 patients experienced severe cardiotoxicity, consisting of major arrhythmias, myocardial ischaemia, reduction of ejection fraction measured with heart radionuclide scan, and were excluded from continuing treatment. Other rIL-2-related toxicities forcing exclusion from the study were severe thrombocytopenia (1 case), and generalised exfoliative dermatitis requiring steroids (1 case). Otherwise, treatment was well tolerated; rIL-2-related toxicities promptly recovered after rIL-2 discontinuation in the majority of cases, and no treatment-related deaths were reported. The half-dose rIL-2 regimen was significantly less toxic in terms of hypotension (P = 0.014), fever (P = 0.014), oliguria (P = 0.042), serum creatinine elevation (P = 0.009) and prothrombin time elongation (P = 0.038).(ABSTRACT TRUNCATED AT 400 WORDS)

B cell activation and human immunodeficiency virus infection. V. Phenotypic and functional alterations in CD5+ and CD5- B cell subsets.

B cell dysregulation is a hallmark of human immunodeficiency virus infection. Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we addressed their individual phenotypic and functional behavior. Seropositive patients with both limited and advanced disease progression had an increased percentage of peripheral blood CD5+ B cells, compared to seronegative controls (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls); however, due to the lymphopenia and reduced number of circulating B cells in infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific activation was also displayed by unstimulated CD5+ B cells. These findings indicate that B cell dysregulation during HIV infection involves both the CD5- and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+ B cells in autoimmune phenomena and IL-10 production, these data reinforce the possibility that B cell dysfunction might be causally involved in AIDS pathogenesis.