Prolegomenon for chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40; thereafter the incidence of CLL increases exponentially with age. CLL is characterized by progressive expansion of malignant CD5+ME+ B-cell clone accompanied by a myriad of cellular and humoral immune defects. Each of them might be linked to different clinically manifested complications such as increasing rate of infections, autoimmune disorders and disturbed immune surveillance against tumour cells. We assume that CLL occurs as a consequence of age-dependent, genetically related functional restrictions of the thymic microenvironment in supporting common lymphoid progenitor cells (CD5+ME+CD4-CD8-) to differentiate into mature T-cell and B-cell descendants. In conjunction with genetic abnormalities developing in B-cell progenitors, presumably expressing P glycoprotein (Pgp+), we postulate that developmentally altered T-cell descendants, along with quantitative imbalance among CD4+, their subsets and CD8+ lymphocytes in the peripheral blood, play an important additional role in facilitating the malignant B-cell clone emergence and in modulating the CLL clinical evolution. Namely, imbalance of any of T-cell-mediated cell interactive homeostatic mechanisms accompanied by imbalance in the production of various cytokines might in CLL influence leukaemic B-cell growth by deregulating inducer (c-myc and p53) and/or suppressor (bcl-2 and mutant p53) oncogenes responsible for the promotion or suppression of B-cell mitogenesis that may in turn further contribute to their impaired differentiation and/or differentiation arrest. In conclusion, CLL might be interpreted as a primary immunodeficiency syndrome developing in elderly population due to gradually evolving restriction of genetically controlled programs in the thymic microenvironment responsible for irregular maturation of common lymphoid progenitor cells that constitutively express CD5 antigen and ME receptor into T-cell and B-cell descendants.

The relevance of multidrug resistance-associated P-glycoprotein expression in the treatment response of B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether expression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with hematologic indices and tumor load in the disease. Furthermore, the change of Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied. DESIGN AND METHODS: In 42 B-CLL patients, of whom 13 were sequentially monitored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp epitopes on peripheral blood lymphocytes was determined by flow cytometry analysis and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. RESULTS: Median RMF values in B-CLL patients were higher than in age-matched controls. Pgp expression did not correlate with any of the hematologic features or clinical stage of the disease. Patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both measured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in comparison to those of non-treated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after treatment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders. This was in contrast to unchanged or even increased RMF values in those patients who did not respond to therapy. INTERPRETATION AND CONCLUSIONS: Our study confirms the importance of quantitative evaluation of Pgp expression by flow cytometry. At the clinical level, cross-sectional, single test evaluation of Pgp is of limited value whereas sequential follow-up values correlate with treatment response.

A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants.

OBJECTIVE: How far the results of randomized controlled studies apply to everyday care cannot be judged without regular measurements of outcomes in daily practice. We report on systematic data from a 3-year naturalistic prospective study on panic disorder-agoraphobic (PDA) patients treated with antidepressants in a setting of routine clinical practice. Our aim is to describe the evolution of PDA in relation to the treatments employed, and to explore demographic and clinical characteristics that might be predictive of outcome. METHODS: 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospective study. We utilized structured and semi-structures instruments, including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination. The main antidepressants used were imipramine (39%), clomipramine (28.5%) and paroxetine (23.3%); only 9% of patients received other antidepressants. RESULTS: 147 patients (45.1%) stayed on medication throughout the entire period of the follow-up. Of those who interrupted the treatment, 38% stayed in remission. The probability of achieving at least one remission during the 3-year follow-up period was 96.5% for PD and 95.9% for Agoraphobia. Relapses after a period of at least 2 months of complete remission were also common, and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1% for PD and 39% for Agoraphobia. The longest period of remission of PD is associated with low severity, medium-lasting course in patients with an onset of the illness in young adulthood. Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior. All three major drugs were reasonably well tolerated (only 9% dropped out because of side effects), with sexual dysfunction and increased appetite being the most common side effects at the last evaluation; in the first phase of the treatment anticholinergic effects and jitteriness were more common with TCAs. CONCLUSION: Both classical antidepressants and paroxetine emerge as a useful treatment in the long-term management of PDA; paroxetine appears particularly useful in PDA patients because it was significantly less likely to induce jitteriness, thereby reducing barriers to compliance.

Anterior tension-free repair of recurrent inguinal hernia under local anesthesia: a 7-year experience in a teaching hospital.

OBJECTIVE: To describe a 7-year experience with recurrent inguinal hernia repair performed mainly with tension-free mesh or plug technique under local anesthesia through the anterior approach, and to evaluate the safety and effectiveness of this method of treatment. METHODS: One hundred forty-five elective and 1 emergency herniorrhaphies for recurrent groin hernia were performed in 141 subjects (134 men and 7 women) with a mean age of 65 years (range 30-89). Concomitant medical and surgical problems were present in 73% and 8% of subjects, respectively. In 28 instances, the relapsed hernia had already been operated on once or twice for recurrence. A traditional hernioplasty had been previously performed in the vast majority of cases (136). Tension-free mesh or plug techniques through an anterior approach under local anesthesia were performed in 144 reoperations. Preperitoneal mesh repair and general or spinal anesthesia were used in all but one case when herniorrhaphy was performed during simultaneous operations. RESULTS: Mean hospital stay after surgery was 1.5 days (range 3 hours-14 days). No perioperative deaths occurred in this series. General complications were one case of acute intestinal bleeding and two cases of urinary retention. Local complications consisted of eight (5.5%) minor complications and one case of orchitis (0.7%) followed by testicular atrophy. In no instance was postoperative neuralgia or chronic pain reported. Two re-recurrences occurred. CONCLUSIONS: Given the low complication rate in this and other reported series and the absence of surgical or general complications described after preperitoneal open or laparoscopic repair and after general and spinal anesthesia, anterior mesh repair under local anesthesia seems to be a low-cost surgical technique that can be safely and effectively used even in a teaching hospital for the treatment of the majority of patients with recurrent groin hernias.

Decision-tree approach to the immunophenotype-based prognosis of the B-cell chronic lymphocytic leukemia.

Use of a nonlinear prediction method, such as machine learning, is a valuable choice in predicting progression rate of disease when applied to the highly variable and correlated biological data such as those in patients with chronic lymphocytic leukemia (CLL). In this work, decision-tree approach to cell phenotype-based prognosis of CLL was adopted. The panel of 33 (32 different phenotypic features and serum concentration of sCD23) parameters was simultaneously presented to the C4.5 decision tree which extracted the most informative of them and subsequently performed classification of CLL patients against the modified Rai staging system. It has been shown that substantial correlation between the percentage of expression of the CD23 molecule on CD19+ B-cells, the level of sCD23, the percentage of CD45RA+, and the absolute number of CD4CD45RA+RO+ T-cells and the clinical stages, exists. The prediction vector, composed of their concatenated values, was able to correctly associate 83% of the cases in the low-risk group (Rai stage 0), 100% of the cases in the intermediate-risk group (Rai stage I and II), and 89% of the cases in the high-risk group (Rai stage III and IV) of CLL patients. Predictivity of this vector was 100%, 95%, and 89%, respectively. In conclusion, from the described analysis, it may be inferred that two processes play important roles in the progression rate of CLL: 1.deregulated function of the CD23 gene in B-cells accompanied by the appearance of its cleaved product sCD23 in the sera; and 2. functionally impaired and imbalanced CD4 T-cell subpopulations found in the peripheral blood of CLL patients.

Hernia repair in elderly patients.

BACKGROUND: This study evaluates a 5-year experience of the management of the most frequent abdominal wall hernias in an elderly population. METHODS: From April 1990 to December 1995, 231 inguinal, 12 femoral and seven umbilical hernias were repaired in 221 patients (mean age 74 (range 66-93) years). Concomitant diseases were present in 157 patients. A mesh repair was performed with 'tension-free' or 'plug' techniques in all but 23 inguinal and two femoral hernia repairs, in which the Bassini or Shouldice procedures were adopted. Ten emergency hernia repairs were performed for strangulation. A total of 232 operations, including four emergency hernia repairs, were carried out under local anaesthesia. RESULTS: There was no perioperative mortality. Acute intestinal bleeding occurred 2 days after surgery in a patient with colonic diverticular disease. Urinary retention occurred once following emergency hernia repair under general anaesthesia and twice after elective hernia repair under local anaesthesia. Local complications included four scrotal haematomas (2 per cent), three wound infections (1 per cent) and one case of orchitis with atrophy after repair of a recurrent hernia. There was one recurrence after a Bassini repair and one after Shouldice inguinal herniorrhaphy. No recurrence was observed after mesh repair. CONCLUSION: Local anaesthetic mesh hernia repair is safe and effective in elderly patients. Age should be no bar to elective hernia repair. This policy should avoid the complications of emergency operation.

Phenotypic analysis of receptor-ligand pairs on B-cells in B-chronic lymphocytic leukemia.

Whole-blood three-color immunofluorescence analysis was used to investigate the role of CD5/CD72 and CD21/CD23 receptor-ligand pair formation on B-chronic lymphocytic leukemia (B-CLL) cells as well as sCD23 and bcl-2 oncoprotein expression in disease progression and activity and total tumor mass in B-cell chronic leukemia (B-CLL) patients. Thirty-four patients with B-CLL and 19 controls were included in the study. The majority of B-cells in B-CLL patients coexpressed CD5 and CD72 as well as the CD23 antigen. Unlike B-cells in B-CLL patients, B-cells in all healthy controls tested had high expression of CD21 antigen. We identified two groups of B-CLL patients according to high (n = 20) or low levels (n = 14) of CD21 expression on CD19+CD23+ B-cells. Only in the patients with high CD21 expression, were sCD23 levels positively correlated with factors known to have prognostic significance in B-CLL (Rai stage and TTM) and could, therefore, be used as a prognostic parameter for these B-CLL patients. Bcl-2 oncoprotein expression did not differ between these patient groups. We presumed that in patients with a lower expression of CD21 antigen, the contribution of the CD21 molecule to homotypic adhesion was lacking. Further studies are necessary to determine the possible association of higher expression of the CD21 antigen with disease progression and the aggressive character of the B-CLL.

[6 years of experience in inguinal and femoral hernioplasty in patients over 65 years of age]. / Sei anni di esperienza di ernioplastica inguinale e femorale nei soggetti con oltre 65 anni di età.

From April 1990 to November 1996, 313 inguinal and 14 femoral hernias were repaired in 295 subjects with a mean age of 74 years (66 to 97). Concomitant diseases increasing the operative risk were present in 206 subjects (70 per cent). A mesh repair was performed with "tension-free" or "plug" techniques in all but 23 inguinal and 2 femoral herniorrhaphies where the Bassini or the Shouldice procedures were adopted. Fifty-two inguinal hernias were recurrent, 11 emergency herniorrhaphies were performed for strangulation. Almost all operations (305), including 9 emergency herniorrhaphies, were carried out under local anaesthesia. There was no perioperative mortality. Acute intestinal bleeding occurred after surgery in a subject with colon diverticulosis. One urinary retention following emergency hernia repair under general anaesthesia and 2 following elective hernia repair under local anaesthesia in 2 subjects with hypertrophy of the prostate were observed. Some episodes of hypotension and/or bradycardia were observed either during or after surgery. Local complications following inguinal hernioplasty were 5 (1.5%) scrotal hematomas, 3 (0.9%) wound infections and 1 case (0.4%) of orchitis with atrophy after repair of a recurrent hernia. There were 1 recurrence after Bassini, 1 after Shouldice, and 1 (0.4%) after mesh inguinal hernioplasty. Using local anaesthesia and a mesh repair elective surgery of inguinal and femoral hernias can be safely and effectively performed in elderly patients. Consequently, early elective surgery should be recommended to avoid the risk of an emergency operation.

[Pregnancy after surgical therapy of obesity. Bibliographic review and our experience with biliopancreatic diversion]. / Gravidanza dopo terapia chirurgica dell'obesità. Revisione bibliografica e nostra esperienza con la diversione biliopancreatica.

BACKGROUND: An increasing number of women in childbearing age are submitted to surgical treatment of obesity; for this reason pregnancy represents a frequent event in operated patients. METHODS: In this study pregnancy in patients with morbid obesity submitted to jejunoileal bypass (JIB) and gastric bypass (GB) are reviewed from the literature and the analysis of our experience with biliopancreatic diversion (BPD) is reported. RESULTS: In 113 pregnancies after JIB reviewed from the literature, the results seem to be debated either about the course of pregnancy or about maternal and neonatal status. The data of literature concerning the pregnancies following GB are less debated but rather slight. One hundred and fifty-two pregnancies after BPD have a complete documentation concerning maternal conditions, modality of outcome and neonatal situation. CONCLUSIONS: Pregnancy occurred in the obese women represents an increased maternal-fetal risk. The excess weight loss, the weight maintenance and the reduced weight changes during pregnancy are an advantage in the operate women who, in any case, need accurate controls of the nutritional status during the whole gestational period. Keeping these cautions pregnancy following surgical treatment of obesity represents an event not only possible but even with less problems than in pregnancy in obese women.

[Surgical treatment of inguinal hernia using a "tension-free" technique and local anesthesia. Initial experience]. / Trattamento chirurgico dell'ernia inguinale con tecnica "tension-free" in anestesia locale. Eperienza iniziale.

Between January, 1991 and December, 1993, 208 subjects with monolateral and 19 with bilateral inguinal hernia were submitted to herniorrhaphy. Thirty-four were recurrent hernias. All but one bilateral hernias were treated at the same time. Eight cases were operated in emergency condition for acute strangulated hernia. Two-hundred and ten operations were performed under local, 17 under general and 1 under spinal anesthesia. Herniorrhaphy was performed in 14 cases with the Bassini and in 38 with the Shouldice technique. In 191 instances the "tension-free" and in 3 the "plug" techniques were adopted utilizing a polypropylene mesh. Following local anesthesia 13 episodes of bradycardia with hypotension were recorded during the operation and 4 in the early postop period. There were no general complications. Two elderly patients developed urinary retention following general anesthesia. Local complications included 6 (2.4%) cases of infection and 4 (1.6%) cases of hematoma of the wound, and 5 (2.0%) cases of edema with infiltration of the cord. Percentage of follow-up at 1, 2 and 3 years was 96, 95, and 93 percent respectively. Five recurrences were recorded: in 1 case following Bassini repair (7.6%), in 2 following Shouldice (5.6%), and in 2 following tension-free (1.5%). Local anesthesia has been confirmed to be well accepted by the patients, effective an safe, especially in the elderly patients with high operative risk. Similarly, the tension-free hernioplasty has been confirmed as a simple, easily reproducible technique, followed by less pain and disability as compared with other types of herniorrhaphies, and more effective mainly in the treatment of recurrent hernia.

Biliopancreatic diversion for obesity at eighteen years.

BACKGROUND: Surgical attempts to treat obesity began because of the discouraging results of conservative medical treatment, which successfully achieved initial weight loss but failed to maintain it. Gastric restrictive procedures, currently the most popular surgical methods for obesity therapy, have proved to be effective in initiating weight loss, but some concerns regarding their long-term efficacy in weight maintenance have arisen. METHODS: Of a total of 1968 obese patients who underwent biliopancreatic diversion since 1976, the last consecutive 1217 underwent the "ad hoc stomach" type of diversion with a 200 cm alimentary limb, a 50 cm common limb, and a gastric volume varying between 200 and 500 ml. Mean age was 37 years old (11 to 69 years), and mean excess weight was 117%. Maximum follow-up was 115 months with nearly 100% participation. RESULTS: In the last half of the series, operative mortality was 0.4% with no general complications and with early surgical complications of wound dehiscence and infection (total, 1.2%) and late complications of incisional hernia (8.7%) and intestinal obstruction (1.2%). Mean percent loss initial excess weight (IEW) at 2, 4, 6, and 8 years was 78 +/- 16, 75 +/- 16, 78 +/- 18, and 77 +/- 16 in the patients with IEW up to 120% and 74 +/- 12, 73 +/- 13, 73 +/- 12, and 72 +/- 10 in those with IEW more than 120%. A group of 40 patients who underwent the original "half-half" biliopancreatic diversion maintained a mean 70% reduction of IEW during a 15-year follow-up period. Specific late complications included anemia (less than 5%), stomal ulcer (2.8%), protein malnutrition (7% with 1.7% requiring surgical revision by common limb elongation or by restoration). Clinical problems from bone demineralization were minimal in the short term and almost absent in the long term. CONCLUSIONS: Biliopancreatic diversion is a very effective procedure but is potentially dangerous if used incorrectly.

Direct cultivation of the causative agent of human granulocytic ehrlichiosis.

BACKGROUND: Human granulocytic ehrlichiosis is a potentially fatal tick-borne infection that has recently been described. This acute febrile illness is characterized by myalgias, headache, thrombocytopenia, and elevated serum aminotransferase levels. The disease is difficult to diagnose because the symptoms are non-specific, intraleukocytic inclusions (morulae) may not be seen, and the serologic results are often initially negative. Little is known about the causative agent because it has never been cultivated. METHODS: We studied three patients with symptoms and laboratory findings suggestive of human granulocytic ehrlichiosis, including unexplained fever after probable exposure to ticks, granulocytopenia, and thrombocytopenia. Peripheral blood was examined for ehrlichia microscopically and with use of the polymerase chain reaction (PCR). Blood was inoculated into cultures of HL60 cells (a line of human promyelocytic leukemia cells), and the cultures were monitored for infection by Giemsa staining and PCR. RESULTS: Blood from the three patients, only one of whom had inclusions suggestive of ehrlichia in neutrophils, was positive for human granulocytic ehrlichiosis on PCR. Blood from all three patients was inoculated into HL60 cell cultures and caused infection, with intracellular organisms visualized as early as 5 days after inoculation and cell lysis occurring within 12 to 14 days. The identity of the cultured organisms was confirmed by immunofluorescence microscopy, PCR analysis, and DNA sequencing. DNA from the infected cells was sequenced in regions of the 16S ribosomal gene reported to differ between the agent of human granulocytic ehrlichiosis and closely related species, including Ehrlichia equi and E. phagocytophila which cause infection in animals. The sequences from all three human isolates were identical and differed from the strain of E. equi studied in having guanine rather than adenine at nucleotide 84. CONCLUSIONS: We describe the cultivation of the agent of human granulocytic ehrlichiosis in cell culture. The ability to isolate this organism should lead to a better understanding of the biology, treatment, and epidemiology of this emerging infection.

[Malignant tumors of the pancreas and periampullary area. Our experience]. / I tumori maligni del pancreas e dell'area periampollare.

The authors analyse and evaluate the clinical records of 45 patients treated in the last 4 years for pancreatic cancer and neoplasm of the bilioduodenapancreatic area, comparing the results with data available in the literature. In the group of patients treated with resection (12 cases), postoperative morbidity and mortality were respectively 28% and 6%, and three-years survival was 22%. The authors discuss particularly about reconstruction ways after duodenopancreatectomy, showing good results after reconstruction by Y loop sec. Roux and pancreato-jejunal anastomosis.

Bloodstream invasion in early Lyme disease: results from a prospective, controlled, blinded study using the polymerase chain reaction.

PURPOSE: The purposes of this study were to determine (1) the optimal techniques for and potential diagnostic usefulness of the polymerase chain reaction (PCR) in early Lyme disease, and (2) the true frequency and clinical correlates of PCR-documented blood-borne infection in the dissemination of Lyme disease. PATIENTS AND METHODS: We performed a prospective, controlled, blinded study of PCR, culture, and serology on fractionated blood samples from 105 patients; 76 with physician-diagnosed erythema migrans and 29 controls. Clinical characteristics of the patients were obtained with a standardized data entry form and correlated with results of the laboratory studies. RESULTS: Only 4 of the 76 (5.3%) patients with erythema migrans were culture positive; however, 14 of 76 (18.4%) had spirochetemia documented by PCR of their plasma. None of 29 controls were PCR or culture positive (P = 0.007, versus patients). PCR-documented spirochetemia correlated with clinical evidence of disseminated disease; 10 of 33 patients (30.3%) with systemic symptom(s) were PCR positive compared to 4 of 43 (9.3%) without such evidence (P = 0.02). PCR positivity was more frequent among patients with each of four specific symptoms: fever, arthralgia, myalgia, and headache (all P < 0.05). A higher total number of symptoms (median 2.5 in PCR-positive patients versus 0 in PCR-negative controls; P < 0.01) and the presence of multiple skin lesions (37.5% of patients with multiple, versus 13.3% of patients with single lesions [P = 0.04] were also correlated with PCR positivity. Patients with both systemic symptoms and multiple skin lesions had a 40% PCR-positivity rate; however, 4 of 42 (9.5%) asympatomatic patients with only single erythema migrans lesions were also PCR positive. In multivariate analysis using logistic regression, the number of systemic symptoms was the strongest independent predictor of PCR positivity (P = 0.004). CONCLUSIONS: PCR detection of Borrelia burgdorferi is at least three times more sensitive than culture for identifying spirochetemia in early Lyme disease and may be useful in rapid diagnosis. PCR positivity significantly correlates with clinical evidence of disease dissemination. Bloodstream invasion is an important and common mechanism for the dissemination of the Lyme disease spirochete.

Modalities of in vitro IgM and IgG production by peripheral blood lymphocytes of chronic lymphocytic leukemia patients and healthy volunteers.

In vitro spontaneous and mitogen (LPS, rIFN alpha and PWM) or cytokine (rIL-2) induced IgM and IgG production by peripheral blood lymphocytes of 15 CLL patients and 16 healthy volunteers has been determined. This study has shown: (1) that there is no difference between healthy donors and CLL patients in respect to level and variability of spontaneous immunoglobulin production by their lymphocyte cultures; (2) that there is no correlation between the percentage of B cells in individual cell cultures obtained from CLL patients and the amount of spontaneously produced IgM or IgG; (3) that there is a correlation between spontaneous in vitro IgM production and IgM content in the serum of the patient; (4) that in CLL patients selective augmentation of IgM production could be obtained after stimulation with PWM or rIL-2, but only in those cultures which spontaneously produce more than 35 ng/ml of IgM and (5) that the number of lymphocyte cultures able to be stimulated to IgM production is about 10 times smaller when they originate from CLL patients than from healthy volunteers. These findings are in line with the view that B cells in CLL patients often do not differentiate due to the insufficiency of factor(s) secreted by their own activated T-cells, but that in essence they follow the same differentiation pathway as normal B-cells.

Transient early metabolic and functional hyperreactivity and late areactivity of lymphocytes in preleukemic AKR mice.

The dynamics of changes in the metabolic and functional activities of thymus, lymph node and spleen lymphocytes and spleen macrophages of AKR mice was examined during the preleukemic period. The MTT colorimetric assay was used to determine the mitochondrial enzyme activity of viable cells, the local xenogeneic GVH reaction and the IL-2 assay for measuring T cell responses, and the IL-1 assay as an indicator of macrophage activity. In the early preleukemic period (at 1.5 months of age), lymphocyte dehydrogenase enzyme hyperactivity was accompanied by a highly increased production of IL-2, positive local xenogeneic GVH reaction and increased IL-1 production. Later on, at the age of 4-5 months, AKR mice demonstrated a progressive decrease in the metabolic activity of lymphocytes, negative local GVH reaction and reduction or lack in IL-2 and IL-1 production. This early hyperreactivity and late, gradually evolving, areactivity of lymphocytes and macrophages was not found in other, non-leukemic strains of mice (RFM, CBA, C57BL).

Functional differences of T cells in B-chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) is a disease characterized by an accumulation of monoclonal lymphocytes of B cell origin. Although the neoplastic process involves the B lymphocyte compartment, phenotypic and functional defects within the T lymphocyte population implicate their possible role in the pathogenesis of the disease. We analyzed the functional and morphological integrity of T lymphocytes from the peripheral blood of 64 patients with B-CLL. The activation of B-CLL T cells after PHA stimulation was determined by measuring [3H]-thymidine incorporation, assessing cell numbers in parallel cultures, and by monitoring the lymphocyte subsets during 9 days of cultivation. Our results indicate the presence of three functionally different populations of T cells in the peripheral blood of B-CLL patients. We present evidence for an increased proliferative potential of T lymphocytes from a group of patients with B-CLL.

The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases.

The roles of age and sex and their relationship to other prognostic factors were studied in 117 chronic myeloid leukaemia (CML) and in 256 chronic lymphocytic leukaemia (CLL) patients. Survival in CML was not related either to age at diagnosis or to sex. In contrast, the CLL patients classified into four age strata (less than 50, 50-59, 60-69, greater than 70 years) had an expected median survival (EMS) of 142, 101, 85 and 33 months respectively (chi 2 for heterogeneity = 35.59, P less than 0.0005; chi 2 for trend = 25.09, P less than 0.0005). Prognostic power was independent of sex, Rai stages, total tumour mass score (TTM), TTM distribution pattern, anaemia, thrombocytopenia, serum immunoglobulins and response to therapy. The relative survival rate (the ratio of patient's EMS and EMS in age- and sex-matched general population) was 0.40 in CLL patients and 0.13 in CML patients. Relative survival was more reduced in older CLL patients than in younger ones (0.37 vs 0.47, respectively), whereas relative survival was less reduced in older CML patients than in younger ones (0.18 vs 0.12, respectively). The results show that the age is a significant independent prognostic factor in CLL but not in CML. The difference in the effects of age on prognosis in CLL and CML most probably reflects the fundamental differences in their respective pathogeneses.