Synthetic thymic fraction 5: effects of high dose administration on circulating lymphocytes in patients.

The synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr; TP-5) corresponding to the active site of the hormone thymopoietin, was given at the dose of 300 mg/m2/day (1 day), higher than the usually administered, to a group of 27 immunodepressed patients in order to determine the tolerability and the immunomodulatory activity. The examination of a series of hematological parameters including counts of differential clustering of lymphocytes by cytofluorimetric analysis was performed 24 hr and 48 hr after treatment, and repeated at different intervals up to 14 days after treatment. TP-5 caused a significant increase of circulating lymphocytes and particularly of CD3+CD4+ and CD3+CD8+ subtypes, peaking at 48 hr and maintaining the increased values up to the last examination on day 14 from treatment. A faster increase (zenith at 24 hr) was observed for CD4+ cells, in comparison with CD8+ cells (zenith at 48 hr). The number of patients that increased total lymphocytes or lymphocyte subset after treatment ranged between 52.6 (CD4+ cells) and 69.2% (NK cells), whereas about 7.7% (NK cells) to 36.9% (CD4+ cells) remained unchanged and a smaller amount of 10.5% (CD4+ and CD8+ cells) or 23.1% (NK cells) showed a decrease greater than 10% of their respective basal value. No significant relationship between responders and non-responders can be found on the basis of previous treatments, cancer type, sex or age.

Effect of marrow processing on hematopoietic cell recovery in bone marrow harvests: focus on filtration.

Bone marrow processing requires a first step of filtration to remove small clots, bone fragments, fat cells and fibrin followed by centrifugation to separate mononuclear cells (MNC). These procedures cause a significant loss of cells potentially including hematopoietic stem cells (HSC). We therefore analyzed the cell recovery and phenotype of various fractions (whole marrow; filtered marrow; MNC collected after centrifugation; bone marrow fragments trapped by filtration) of bone marrow harvests (BMH) from patients with different hematological malignancies undergoing autologous bone marrow transplantation. Analysis of 25 BMH showed that the mean percentage of WBC and MNC recovered after filtration was respectively 92.28 +/- 7.42% and 92.3 +/- 9.05% of the original BMH while after centrifugation the percentage was 20.23 +/- 6.47% and 75.7 +/- 12.81%. The percentage of cells present in the tissue fragments trapped in the filters obtained from five BMH was only 3.93 +/- 1.25% (WBC) and 5.65 +/- 2.2% (MNC) of those originally present in the harvest. Phenotypic analysis performed on the same samples showed that there is no selective loss of MNC or CD34+ cells in the filtration process. Our data indicate that processing of BMH, in particular filtration of tissue fragments, does not affect the recovery of HSC.

Reduced lymphocyte subpopulations in patients with advanced or disseminated melanoma.

BACKGROUND: Studies have revealed many features of lymphocyte behavior in patients with malignant melanoma, but there are conflicting results. OBJECTIVE: The aim of this study was to measure with easily reproducible assays the circulating lymphocytes and other immunologic aspects in 33 patients with advanced or disseminated malignant melanoma (MM). METHODS: The following variables were measured: circulating monocytes; total lymphocytes; B (CD19) and T-cell subpopulations; CD3, CD4, and CD8, natural killer cells (anti-Leu-7+ or CD57 and anti-Leu-11+ or CD16) (cytofluorimetry); plasma levels of IgG, IgA, IgM, and IgE; complement fractions 3, 4, and 1Q; antibodies against foreign microorganisms (AaM) (adeno, herpes simplex, herpes zoster, measles, parotitis, cytomegalo, Epstein-Barr, and rubella viruses) and Toxoplasma; and cutaneous delayed hypersensitivity (CDH) to recall antigens (tetanus, diphtheria, Streptococcus, tuberculin, Proteus, Trichophyton, and Candida). We also studied 96 healthy persons, matched for age and geographic location, who were tested on the same days as the patients. RESULTS: In MM the number of total lymphocytes and subsets CD19, CD3, CD4, and CD8 was decreased from 25% to 40% (p < 0.001). The CD4/CD8 ratio increased (22%, p < 0.005) because of the relatively greater decrease of CD8. The CD57 and CD16 cells (expression of natural killer lymphocytes) were consistently reduced (30%; p < 0.002 to p < 0.003). C3 serum level was increased (30%; p < 0.001). Immunoglobulins, CDH, AaM, and all other tests were the same in the two groups. CONCLUSION: The single most important result seems to be a reduction of CD57 and CD16 cells in patients with advanced MM.

Inappropriate emergency test ordering in a general hospital: preliminary reports.

An assessment was made on emergency laboratory test ordering at Udine General Hospital (Italy) to investigate the reasons for the excessive number of requested tests. All the orders for emergency laboratory tests during one week in June 1990 were studied. For each test the time of the order was recorded for every day of the week. The most important aspect of our investigation is the distribution of the orders during the day: in fact, test orders reached two peaks, the upper between 7 and 11 a.m., and the lower between 3 and 6 p.m. The analysis of the record cards showed that 42% of the orders were inappropriate. These preliminary findings were very useful in making the consensus on a Quality Assurance program easier, to improve the use of the Emergency Laboratory by doctors and nurses. Some preliminary results in the Emergency Medicine Department confirmed the validity of this program.

[Influence of radiotherapy on lymphocyte subpopulations]. / Influenza della terapia radiante sulla popolazione linfocitaria.

The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.

[Idiopathic monoclonal gammopathy. Long-term study of 313 cases]. / Gammopatia monoclonale idiopatica. Studio a lungo termine di 313 casi.

The records of 519 patients with a paraproteinaemia who where examined at our institutions before January, 1, 1983, were reviewed. After patients with multiple myeloma, macroglobulinemia, amyloidosis, lymphoma or related diseases had been excluded, 363 cases remained which fulfilled the criteria for a diagnosis of idiopathic monoclonal gammopathy (IMG). Also excluded were the cases in which follow-up efforts failed and those in which the paraprotein had disappeared. A long-term study was thus possible in 313 patients with IMG. They were arbitrarily subdivided into two groups: 213 patients with a follow-up of 5-8 years and 100 patients whose follow-up was longer than 8 years. Fourteen per cent of the patients from the former group and 18 per cent from the latter developed a malignant B cell dyscrasia, on the average this event becoming clinically detectable after 63 months (27-138 months) from initial recognition of the paraprotein. A retrospective analysis of the clinical data at the diagnosis of IMG, revealed that none of the patients could have been identified in advance in whom a malignant transformation later occurred.

Monoclonal-oligoclonal immunoglobulins in HTLV III infected subjects: HTLV III-induced or HTLV III-associated?

Sera from 55 patients with positivity for anti-HTLV III antibodies, including 24 "healthy" subjects, 29 LAS and 2 AIDS, were examined by means of high resolution agarose gel electrophoresis and immunofixation, in order to evaluate the occurrence of monoclonal-oligoclonal immunoglobulin patterns. Monoclonal-oligoclonal immunoglobulins were found in 20.8% of "healthy" subjects and in 72.4% of LAS patients. Furthermore, a lower but significant prevalence of monoclonal-oligoclonal immunoglobulins was found in a control group including patients with high-titre positivity for anti-CMV and anti-EBV antibodies. Considering the consistent association between EBV-CMV and HTLV III infection, it is concluded that at least a part of monoclonal-oligoclonal immunoglobulins found in LAS-AIDS patients are likely to be induced by these associated viral infections. On the other hand, the finding of monoclonal-oligoclonal immunoglobulins in "healthy" HTLV III-positive subjects points out a possible direct stimulatory effect of HTLV III on B-cell lineage.

Monoclonal antibody defined T cell subsets in primary and secondary Sjögren's syndrome.

Using monoclonal antibodies of the OKT series we studied the blood T lymphocyte subsets of 12 patients with Primary Sjögren's Syndrome, 15 with Rheumatoid Arthritis associated Sjögren's Syndrome and 10 normal controls. We found a marked reduction of T lymphocytes both in Primary and Secondary Sjögren's Syndrome compared with normal controls (p less than 0.001). While no difference was noted in the number of helper-inducer T cells between Primary and Secondary Sjögren's Syndrome, a more important decrease of suppressor-cytotoxic cells was demonstrated in Secondary Sjögren's Syndrome (p less than 0.01). These data may contribute to a better understanding of the disease.

Identification with monoclonal antibodies of T-cell subsets in peripheral blood and ascitic fluid of patients with alcoholic hepatic cirrhosis.

In an attempt to investigate an aspect of the immunoregulatory mechanisms operating in alcoholic hepatic cirrhosis with ascites we have enumerated T-cell subsets in the peripheral blood and ascitic fluid of 16 patients with this disease. The peripheral blood analysis revealed a reduction of OKT3+, OKT4+ and OKT8+ cells compared to those of the control group (p less than 0.001) and an increase of OKT4+/OKT8+ ratio. In the ascitic fluid the OKT4+/OKT8+ ratio, compared to that of the peripheral blood, was decreased (p less than 0.001) because of increase of OKT8+ cell proportion. We suggest that the sequestrated splanchnic OKT8+ subset might be represented by suppressor lymphocytes transuding from the liver.

In vitro synthesis of human IgE: reappraisal of a 5-year study.

In the last 5 years some models of human IgE production in vitro have been investigated in our laboratory. Spontaneous IgE synthesis was found in cultures of B cells from most patients with atopic dermatitis or atopic patients with multiple sensitivities and from some patients with pollenosis, but only during the pollination period. A small and variable increase of the spontaneous IgE synthesis was induced by soluble factor(s) produced by T cells from patients with severe atopy. Selected helper T cell clones were also able to induce IgE synthesis in vitro by both atopic and normal B cells.

[T lymphocyte subpopulations in rheumatoid arthritis]. / Studio di sottopopolazioni linfocitarie T nell'artrite reumatoide.

The study of T lymphocyte subpopulations defined by monoclonal antibodies in a group of patients with rheumatoid arthritis and a control group indicated no significant differences in the percentages of total T lymphocytes (OKT3+) or helper-inducer lymphocytes (OKT4+). However there was a significant diminution in suppressor-cytoxic lymphocytes (OKT8+) in patients with active forms of the disease. This diminution led to an increase in the proportion of OKT4+/OKT8+ in patients with active R.A. forms compared to both those in remission and the control group.

[Salivary immunoglobulins G, A and M in liver cirrhosis]. / Immunoglobuline salivari G, A ed M nella cirrosi epatica.

Mixed saliva of the patient with cirrhosis of the liver contains often large quantities of immune globulins. IgA and M transport is facilitated, but whereas IgA globulins are present in all cases, the IgM appear in the saliva only where plasma concentration is greater than 200 mg %. Owing to a simple passive diffusion mechanism, the IgG reach high saliva levels in all subjects studied.

Effect of chemotherapy on the anion gap in multiple myeloma.

In 12 myeloma patients responding to chemotherapy (7 IgG and 5 IgA), we studied the effect on the anion gap of a 50% reduction in the serum paraprotein concentration. In contrast to the pretreatment anion gap which was decreased in IgG myeloma and increased in IgA myeloma, the value calculated when the paraprotein spike was halved showed a tendency towards normalization in the former type of myeloma, whereas it appeared as quite normalized in the latter. Our results lend further support to the conceptions that IgG and IgA paraproteins behave in the serum as cations and anions, respectively, and that serial determinations of the anion gap may be of value for monitoring the response to treatment in patients with multiple myeloma.