Residual low-level viral replication could explain discrepancies between viral load and CD4+ cell response in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

We report the evolution of chronic infection with human immunodeficiency virus type 1 (HIV-1) in a patient treated with stavudine plus didanosine, whose CD4+ lymphocyte count progressively decreased, despite a sustained plasma viral load <20 copies/mL. After 12 months of therapy, treatment was switched to zidovudine plus lamivudine plus nelfinavir. CD4+ T cell count decreased from 559 x 10(6)/L at month 0 to 259 x 10(6)/L at month 12. Plasma viral load decreased from 21,665 HIV-1 RNA copies/mL at baseline (month 0) to <20 copies/mL after 1 month of therapy with stavudine plus didanosine, and remained below 20 copies/mL until month 12, but always >5 copies/mL. Viral load in tonsilar tissue at month 12 was 125,000 copies/mg of tissue. After the change to triple-drug therapy, the plasma viral load decreased to 5 copies/mL, the CD4+ T cell count increased to 705 x 10(6)/L, and the viral load in tonsilar tissue decreased to <40 copies/mg of tissue at month 24. A low level of HIV-1 replication could explain the lack of immunologic response in patients with apparent virological response.

Bone marrow histopathologic patterns and immunologic findings in B-chronic lymphocytic leukemia.

In 82 patients with B-chronic lymphocytic leukemia, the correlations between the histopathologic bone marrow patterns (interstitial, nodular, mixed, and diffuse), serum immunoglobulin (Ig), and blood B-lymphocyte levels and T-lymphocyte levels have been analyzed. The most commonly lowered Ig class was IgM (43% of cases) followed by IgA (35%), and IgG (10%). There was a trend to a more frequent decrease of Ig levels when "advanced" bone marrow patterns (mixed + diffuse) were compared with the earlier ones (interstitial + nodular). The frequency of such a decrease was statistically significant for IgA class (P less than 0.01). The absolute number of blood T-lymphocytes was increased in the diffuse pattern (P less than 0.01).

Complement activation in septic shock due to gram-negative and gram-positive bacteria.

Whole serum complement (CH50) and C3, C4, and C3PA plasma values were studied in 48 patients: 9 with nonseptic shock; 20 with sepsis; 14 with septic shock caused by gram-negative bacteria; 5 with septic shock caused by gram-positive bacteria. All were compared with a control group of 25 healthy individuals. Determinations were made upon admission and again 48 and 96 h later. No significant differences in complement values were found between the patients with nonseptic shock and the control group. In the patients with sepsis, decreased CH50 (p less than 0.001) and increased C3PA (p less than 0.02) values were observed, while C3 and C4 remained unaltered. In the patients with septic shock, markedly decreased levels of CH50, C3, and C4 were seen (p less than 0.001, and p less than 0.001, and p less than 0.001, respectively) without changes in C3PA levels. There were no differences between septic shock due to gram-negative and gram-positive bacteria, or between patients who died and those who survived. After 96 h, the altered values returned to the normal range. This underlines the transitory activation of the complement system through the classic pathway and suggests its possible role in the pathogenesis of septic shock in man.

[Circulating immune complexes-like material and complement in rheumatoid arthritis and ankylosing spondylitis (author's transl)]. / Inmunocomplejos circulantes y complemento en la artritis reumatoidea y en la espondilartritis anquilosante.

Circulating immune complexes (IC) in 52 rheumatoid arthritis (RA) seropositive, 25 RA seronegative and 32 ankylosing spondylitis (AS) patients were assayed by two methods: 1) precipitation with a final 2% polyethylene glycol (PEG) concentration with immunoglobulins (Igs) quantitation in the precipitate and 2) the ability of IC to consume complement, evaluating conversion products from human C3 by bidimensional rocket immunoelectrophoresis. CH50, C3, C4, C3PA and circulating C3 conversion products were quantitated. IC precipitates with 2% PEG contained three classes of Igs: IgG, IgM and IgA, the latter being the most rare. In the control group Igs level precipitated with 2% PEG were: 2% PEG-IgG 2.5 mg/100 ml +/- 2; 2% PEG-IgM 0.72 mg/100 ml +/- 1.09; 2% PEG-IgA 0.04 mg/100 ml +/- 0.18. With 2% PEG IC-like material was detected in 58.5% of RA seropositive patients but none generated C3 conversion products. With neither methods was IC-like material detected in the RA seronegative group and none with 2% PEG in AS, either. However, in the latter, 21.8% generated C3 conversion products and 18.7% circulating C3 conversión products. In the RA seropositive patients no correlation was observed between the levels of 2% PEG-IgG and 2% PEG-IgM and the titre of antinuclear antibodies (ANA) nor between 2% PEG-IgG and that of IgG in serum. However, there was a low correlation between 2% PEG-IgM and that of IgM in serum and between 2% PEG-IgG and 2% PEG-IgM with rheumatoid factor (RF). It should be stressed that the value of the PEG method in the detection of IC-like material must be reconsidered, since using a 2% final concentration and a specific evaluation of Igs and complement components in the precipitate, it may be a method easy to perform and useful for clinical purposes.

[Absence of antiDNA antibodies in the cryoglobulins of a case with sicca syndrome (author's transl)]. / Ausencia de anticuerpos antiDNA en las crioglobulinas de un sicca syndrome.

Cryoglobulins are serum immunoglobulins (immunocomplexes) that precipitate in the cold and redissolve on warming. Cryoglobulins from patients with several diseases showed the presence of antiDNA antibodies when previously underwent incubation in acid buffer. The possibility that antiDNA antibodies might constitute the immunocomplexes found in patients with systemic lupus erythematosus and with other connective tissue diseases is suggested. Negative findings in relation to the presence of antiDNA antibodies in cryoglobulins of a case with sicca syndrome are reported.

[Mixed essential cryoglobulinemia. Report of five cases (author's transl)]. / Crioglobulinemia mixta esencial. Communicación de cinco casos.

Cryoglobulins are serum immunoglobulins which precipitate in the cold and redissolve on warming at 37 degrees C. According to its immunochemical composition three different types have been described. Cryoglobulins have been reported associated with hematologic disorders, systemic diseases, infectious conditions, and diseases of the liver and kidneys. There is also an idiopathic variant called essential cryoglobulinemia. Five patients (four males) with mixed essential cryoglobulinemia are reported. Common clinical manifestations included fever, articular symptoms, purpura, glomerulonephritis, Raynaud's phenomenon, erythematomacular cutaneous eruption, polyneuritis and abdominal pain. Serum activity of rheumatoid factor has been detected in three cases; in other three decreased levels of serum complement have been found. Serum HBsAg was negative in four cases (passive hemagglutination technique). It is possible that all cases of mixed essential cryoglobulinemia may correspond to bacterial, viral or fungal occult infections.

[Hereditary angioneurotic edema: study of serum complement and therapeutic trial with tranexamic acid (author's transl)]. / Edema angioneurótico hereditario: estudio del complemento y ensayo terapéutico con ácido tranexámico.

Three familial generations (five members with hereditary angioneurotic edema) have been evaluated under clinical and immunological standpoints. A therapeutic trial with tranexamic acid was carried out. The five members with hereditary angioneurotic edema showed: decreased values of total hemolytic activity (CH50), deficit of C4 (between 8 and 23 percent of the normal value), and normal levels of C3 and C9. C3PA was normal in four members and decreased in one. Asymptomatic familial members had normal serum complement levels; only three cases showed diminished values of CH50, C4, C-1-INH and C3PA. Therapeutic trial with tranexamic acid demonstrated the usefulness of this agent in the treatment of angioneurotic edema; it showed slighter adverse reactions than those derived from other therapeutic modalities. Screening of asymptomatic familial members is pointed out in order to detect low plasma values of C1-IHN.

[Cryoglobulins and liver disease. Study of 34 cases (author's transl)]. / Crioglobulinemia en hepatopatías. Estudio en 34 pacientes.

Cryoglobulins are immunoglobulins characterized by precipitating when serum is cooled and redissolving when serum is heated. There is strong evidence to consider mixed cryoglobulins as circulating immunocomplexes, and various investigators have applied the precipitating physical property as a method to isolate immunocomplexes. In the recent years some authors have reported the presence of cryoglobulins in acute and chronic liver diseases of diverse etiology. This study investigates the presence of cryoglobulins in 34 patients with different liver diseases. Mixed cryoglobulins were detected in eight patients (23.5 percent), but only three of them had clinical symptoms attributable to the existence of cryoglobulins. In relation to the etiology of the liver disease, the highest frequency has been found among patients with hepatopathies of undetermined origin.

[Cryoglobulins in systemic and rheumatological diseases. Report of 70 cases (author's transl)]. / Crioglobulinas en enfermedades sistémicas y reumatológicas. Estudio en 70 casos.

Cryoglobulins are immunoglobulins characterized by precipitating when serum is cooled and redissolving when serum is heated. There is strong evidence to consider mixed cryoglobulins as circulating immunocomplexes. Cryoglobulins have been demonstrated in association to hematologic, hepatic, lymphoproliferative, autoimmune and infectious conditions. There is also an essential or idiopathic variant. The present report studies a series of 70 patients with several rheumatic and systemic diseases, and a group of ten patients with cutaneous vasculitis. Significant levels of cryoglobulins have been detected in nine cases (overall incidence 12.8 percent). The diagnoses corresponding to these patients were as follows: systemic lupus erythematosus in three cases, dermatopolymyositis in three cases, Sjögren's syndrome in two cases, and Wegener's granulomatosis in one case. Cryoglobulins could not be demonstrated in patients with rheumatoid artritis, sclerodermia, periarteritis nodosa, cutaneous vasculitis, Reiter's syndrome, ankylosing spondilitis and acute articular rheumatism. Among patients with systemic lupus erythematosus a good correlation has been observed between the presence of serum cryoglobulins, the activity and severity of the diseases and the decrease of serum complement levels.

[Etiologic diagnosis of pneumoccocal pneumonia by counterimmunoelectrophoresis (author's transl)]. / Diagnóstico etiológico de la neumonía neumocócica por contrainmunoelectroforesis.

The antigenic composition of the pneumoccocal capsule and its easy detection by counterimmunoelectrophoresis led us to carry out a comparative study of this method and the results obtained from cultures. A series of 159 patientes with suspected bacterial pneumonia were included in the study. Blood cultures were prepared for all of the patients; sputum cultures were practiced on 35 and cultures of pleural fluid on 32. Serum from all of the patients, urine from 104, sputum from 34, and pleural fluid from 16 were analyzed by counterimmunoelectrophoresis for pneumoccocal antigen. This method was particularly useful for detecting the germ in sputum and pleural fluid. Furthermore, a higher number of positive indexes in serum were obtained by counterimmunoelectrophoresis than by blood cultures (p less than 0.01). This was also true for tests with sputum and pleural fluid. Urine tests resulted in an even greater number of detections. Counterimmunoelectrophoresis is thus a simple, quick method for detecting pneumococcus and is especially useful when accompanied by cultures tests, since they are complementary. We were able to discover a positive indication of penumoccocus in bacterial pneumonia in 39.6 percent of cases with this technique, as opposed to 15 percent using cultures alone.

A new case of gamma-heavy chain disease.

The first case of gamma-heavy chain disease described in Spain is here reported. The patient, a 36-year-old woman, presented fever, enlarged regional lymph nodes, and hepatosplenomegaly, without bone marrow abnormalities but with lymphopenia. Serum electrophoresis did not disclose any M-component. The abnormal gamma-chain protein had a alpha2-globulin mobility and was immunochemically related to the Fc fragment. It belonged to the IgG 4 subclass, its molecular weight was about 60,000. Proteinuria was minimal but the electrophoresis of concentrated urine showed a homogeneous peak of alpha2-globulin mobility constituted by the gamma-chain fragment. Biopsy of an axillary lymph node disclosed features of immunoblastic sarcoma. The course was malignant, resulting in death in 8 months.