Direct determination of benzalkonium chloride in ophthalmic systems by reversed-phase high-performance liquid chromatography

High-performance liquid chromatography has been used to quantitate benzalkonium chloride (alkylbenzyldimethylammonium chloride) in complex ophthalmic formulations at or below concentration levels of 50 ppm. The method involves a one-step dilution for sample preparation and direct injection; therefore, recovery and/or conversion problems are nonexistent. The assay is quick, specific, reproducible, and simple. This new approach makes routine determinations far simpler than previous methods and is especially useful for product stability studies and quality control procedures.     

SPECT follow-up of cerebral blood circulation after stroke]

rCBF SPECT investigations with 99mTc-HMPAO were performed in 22 completed ischemic stroke patients on average 2.5, 16.8 and 38.0 days after stroke onset. As control group, 12 neurologically healthy volunteers were examined with the same method. The overall sensitivity of the rCBF SPECT method in the detection of cerebral blood flow abnormalities was 91%, with a specificity of 83% and an accuracy of 88%. The rCBF study was highly effective, particularly in the acute phase of the disease. Regional increased tracer uptake or a false normal 99mTc-HMPAO distribution due to the developing hyperemia mostly complicated the rCBF image interpretations in the subacute period. In the chronic phase, the spatial resolution of the SPECT system limited the detection of the continuously retracted stroke lesions.     

CD8 expression on B cells in chronic lymphocytic leukemia: a case report and review of the literature

The expression of CD8, a restricted T-cell antigen, on B cells in B chronic lymphocytic leukemia is rare, and its significance, if any, remains unknown. We report herein a patient with B chronic lymphocytic leukemia in whom CD8 was strongly expressed on all B cells, both in the bone marrow and peripheral blood. The patient required no therapy for 6 years after being diagnosed as having B chronic lymphocytic leukemia. Then, when the disease progressed, he was treated with conventional doses of fludarabine phosphate (25 mg/m(2) daily for 5 days), but unlike other patients with B chronic lymphocytic leukemia he tolerated this therapy poorly. He received a total of only 4 series of fludarabine therapy, and following each course of treatment, he developed considerable myelosuppression. After the fourth course of therapy, his bone marrow failed to show any evidence of regeneration, and he died as a result of intercurrent respiratory tract infection 1 month after his last dose of fludarabine was given.     

Plasminogen activators in human malignant melanoma

Metastatic malignant melanomas from 16 patients, extracted with Triton X-100, were analyzed for plasminogen activator activity by azocaseinolysis . In 6 cases tumor explants were set up also in short-term organ culture, and the rate of plasminogen activator secretion into the culture medium was determined. Both the extractable activator content [8.66 +/- 7.8 "Committee on Thrombolytic Agents" (CTA) U/g tissue] and the activator secretion rates (0.90 +/- 1.6 CTA U/g/hr) were low in comparison with values for other human tumors. In addition to the activity, the type of plasminogen activator also was determined by immunoinhibition with goat antihuman urokinase antibody in the azocaseinolytic assay, as well as by sodium dodecyl sulfate (SDS) gel electrophoresis followed by zymography on fibrin-agar, in the presence and absence of antibody. On the average, 77% of the activator activity was of the urokinase type in the extracts, and 90% in the culture fluids. Immunoperoxidase reaction for the detection of urokinase showed this enzyme to be localized mainly in the cell membrane of the melanoma cells; stromal elements showed no specific staining. These results are of interest in view of the findings made recently by investigators in several laboratories that in all but one of the melanoma cell cultures derived from metastatic human tumors, only the vascular type ("tissue activator") was cell associated or was secreted into the culture medium. The possible reasons for this discrepancy are discussed.     

Regional cerebral blood flow changes in schizophrenic patients detected by SPECT studies under resting and active conditions]

Brain SPECT studies in schizophrenia revealed changes in regional cerebral blood flow (rCBF). The rCBF changes can be detected more accurate by activating tests. The aim of this study was to assess rCBF changes under resting and activation condition by the Raven test. Four control patients (2 male, 2 female, average age 45 years, 26-57 years) and 11 chronic, treated schizophrenic patients (4 male, 7 female, average age: 46 years, 33-56 years) were studied in two HMPAO brain SPECT sessions, 48 hours apart, both resting and during activation task. The images were evaluated visually and semiquantitatively. Under resting condition in the control group, there were no significant rCBF changes. In the Raven activation test, a significantly higher blood flow in the prefrontal region was seen (p < 0.05). The schizophrenic group had a significantly lower rCBF in the temporal region under resting condition (p < 0.05): four patients displayed left, 4 right temporal hypoperfusion and 3 exhibited no rCBF abnormality. In the Raven activation tests 5 patients had prefrontal hyperperfusion, and the remaining 6 patients had no such activation answer. Five patients had hypoperfusion in the temporal region. In our sample, patients with chronic schizophrenia displayed significant temporal hypoperfusion. Moreover the chronic schizophrenic group exhibited a poor response to prefrontal activation compared to the control group.     

IgA glomerulonephritis

Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.On the basis of a lecture given at the XXIIIrd Itinerary Congress of the Transdanubian Section of the Association of Hungarian Internists, held at Gyr on 18th June, 1976. Supported by the Scientific Research Council, Ministry of Health, Hungary (3-18-0304-03-2/H).     

Paraneoplastic thrombocytosis in gastrointestinal cancer

It has been demonstrated recently in several solid tumors that thrombocytosis at diagnosis may correlate with tumor invasion, metastatic progression and worse outcome. Several details of the pathomechanism of the relationship of thrombocytosis and cancer have been elucidated; however, the complete process is not clearly understood. Several hypotheses have been proposed. Recently, it was suggested that in ovarian cancer elevated IL-6 production by the tumor may induce increased megakaryopoiesis via hepatic thrombopoietin production leading to thrombocytosis. The importance of the prognostic power of elevated platelet count is still debated in gastrointestinal cancer. The aims of this review were to evaluate the prognostic significance of thrombocytosis in gastrointestinal tumors, to see whether clinical practice confirmed the hypotheses and to reveal the causes of the inconsistent findings.     

The role of fibrinolysis in the therapy of peripheral vascular disease

In vivo thrombolytic studies in stumptailed monkeys indicated that pentoxifylline potentiates thrombolysis induced by urokinase activated human plasmin. Pentoxifylline as well as prostaglandin E1 released plasminogen activators and activated the fibrinolysin system. From this point of view pentoxifylline and prostaglandin E1 synergized with each other. Pentoxifylline potentiated the thrombolytic effect of prostaglandin E1 in vivo.     

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.