Migration inhibition factor activity in sera of patients with chronic lymphatic leukemia.

Migration inhibition factor (MIF) activity, expressed as a migration index, was studied in the sera of 48 chronic lymphatic leukemia (CLL) patients and 48 healthy controls. MIF activity was detected in the sera of 50% of the CLL patients. The medical condition of patients in advanced clinical stages (III and IV) and with detectable MIF activity was more stable (after 18-mo follow-up) than was that of the patients in advanced stages but without detectable MIF activity. No relationship was found between the clinical stage of the disease, absolute lymphocyte count, and MIF activity.

The mechanism of benign hereditary neutropenia.

Benign familial (hereditary) leukopenia and neutropenia (BFLN) have been reported in some ethnic groups, including black Americans and Yemenite Jews. The bone-marrow response of 34 Yemenite Jews (with and without neutropenia) to an intravenous injection of 200 mg of hydrocortisone sodium succinate was studied and compared with the response of 18 healthy control subjects. The mean +/- SEM of the increments in polymorphonuclear cells (PMNs) following injection of hydrocortisone in Yemenite Jews (2,413 +/- 245/mm3 in neutropenic subjects and 2,187 +/- 343/mm3 in nonneutropenic subjects) were significantly lower than in the control subjects (4,431 +/- 467/mm3), without significant differences among the subgroups of the Yemenite Jews. The decreases in monocytes, lymphocytes, and eosinophils were similar in all groups. No correlation was found between baseline PMN levels and the increments following hydrocortisone administration. These results suggest a lowered bone-marrow response to hydrocortisone in subjects with BFLN, indicating some defect in PMNs release from the bone-marrow storage pool to the peripheral blood. It seems that this defect characterizes all members of the ethnic group, whether they have "overt" neutropenia or not.

Fatal peripheral neurolymphomatosis after remission of histiocytic lymphoma.

A 32-year-old woman with histiocytic lymphoma was in complete clinical remission after two courses of chemotherapy, when peripheral neuropathy developed fulminantly. Abnormalities included facial nerve paralysis, dysphagia, quadriparesis, myalgia, and incontinence. She died 10 days after onset of these symptoms. Postmortem examination revealed infiltration of peripheral nerves by lymphomatous cells with no involvement of meninges, brain, lymph nodes, or other organs. Differences in the blood-brain barrier of peripheral and central nervous system are suggested: The peripheral barrier may be more penetrable by malignant histiocytes or less permeable to cytotoxic drugs. Intrathecal chemotherapeutic drug instillation and irradiation may be beneficial.

Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis.

The long-term pattern of prednisone-induced leukocytosis was examined in 80 patients. Our results disclosed an extremely variable leukocytic responses, in which the white blood cell count surpassed 20,000/mm3 as early as the first day of treatment, an increase that persisted for the duration of therapy. Although the degree of leukocytosis was related to the dosage administered, it did appear sooner with higher doses. Leukocytosis reached maximal values within two weeks in most cases, after which the white blood cell count decreased, albeit not to pretreatment levels. The leukocytosis was attributed predominantly to a rise in the polymorphonuclear white blood cells, a phenomenon that coincided with monocytosis, eosinopenia and a variable degree of lymphopenia. It can be concluded that even small doses of prednisone, administered over a prolonged period of time, can induce extreme and persistent leukocytosis. This observation is of consequence especially when infection is suspected, particularly in an immunocompromised host. However, a shift to the left in the peripheral white blood cells, i.e., more than 6 percent band forms, and the appearance of toxic granulation may assist in the differential diagnosis between infection, in which the latter are observed, and corticosteroid-induced leukocytosis, in which they are rare.

Serum cobalamin and transcobalamin levels in systemic lupus erythematosus.

PURPOSE: The purpose of this study was to assay serum cobalamin levels in patients with systemic lupus erythematosus (SLE) as there are few case reports on the association of pernicious anemia and SLE. PATIENTS AND METHODS: Serum cobalamin levels were assayed in 43 female SLE patients by a radio-dilution assay using purified intrinsic factor. RESULTS: Cobalamin levels were found to be significantly lower in the SLE group compared with a normal control group, eight of whom (18.6%) had serum cobalamin levels equal to or lower than 180 pg/mL (mean: 129.25 +/- 40.05 pg/mL). None of the SLE patients had been found to have pernicious anemia. The transcobalamin II level and unsaturated vitamin B12 binding capacity, but not the cobalamin level, were positively correlated with SLE activity. CONCLUSION: Our results may indicate a subtle cobalamin deficiency in SLE patients without pernicious anemia.

Native valve Staphylococcus epidermidis endocarditis: report of seven cases and review of the literature.

This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis.

Tear calcium and magnesium levels of normal subjects and patients with hypocalcemia or hypercalcemia.

Tear calcium and magnesium levels were measured in eight patients with hypercalcemia and two patients with hypocalcemia and compared to that of 72 subjects with normal serum calcium and magnesium levels. No correlation was found between tear and serum calcium and magnesium levels. Tear calcium level has no diagnostic importance.

Possible role of fibrinogen in the aggregation of white blood cells.

In order to verify whether leukocyte aggregation correlated with aggregation of other cellular elements during inflammation, we examined the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood and red cell aggregation. Correlation was found to be significant as was the correlation between LAA and fibrinogen, and with the fibrin/fibrinogen degradation products concentration during various inflammatory states. In vitro leukocyte aggregation was decreased when the cells were suspended in autologous heat defibrinogenated plasma as compared to cells suspended in autologous native plasma. Heat aggregated fibrinogen but not native fibrinogen caused leukocyte aggregation in vitro. Finally, Arvin defibrinogenation in rabbits reduced the state of LAA in endotoxinemic rabbits. Integrating all this information, we assume that fibrinogen participates not only in the aggregation phenomena of red cells and platelets, but also in those of leukocytes.

Human lupus monoclonal autoantibodies bind to Raji cells.

Seven of 60 human monoclonal anti-DNA autoantibodies derived from 3 patients with SLE were shown to bind to Raji cells by radioimmunoassay. The binding of the lupus autoantibodies to the Raji cells in solution was not affected by prior incubation of the cells with DNase. Preincubation of the monoclonal autoantibodies with polynucleotides and cardiolipin, resulted in significant inhibition which correlated with the direct binding characteristics of these antibodies. Previous results with mouse IgG monoclonal anti-DNA antibodies supported by our results with human IgM anti-DNA autoantibodies suggest caution in interpreting analyses of immune complexes of sera containing anti-DNA antibodies entailing Raji cells.

Coincidence of sarcoidosis and amyloidosis.

Amyloidosis was diagnosed in a patient with sarcoidosis. There was no evidence of any other disease known to be associated with amyloidosis. The joint occurrence of amyloidosis and sarcoidosis appears to be extremely rare, and to our knowledge, this is the second such patient to be reported. Whether the association of the two diseases in this patient represents a causal relationship remains an open question.

Diagonal ear lobe crease and coronary risk factors.

The prevalence of ear lobe crease (ELC) was determined in 421 patients with myocardial infarction (MI) and in 421 controls. A higher prevalence (p less than 0.05) of ELC was found in MI patients (77 percent) in comparison to controls (40 percent), regardless of age. In addition, a higher prevalence was found in patients in whom MI was combined with diabetic retinopathy or hypertension, and in Ashkenazi Jews compared to non-Ashkenazi Jews. Ear lobe biopsies in 12 subjects revealed tears of the elastic fibers in all subjects with ELC, and prearteriole wall thickening in subjects with MI and/or ELC, but not in the 2 subjects with neither MI nor ELC. The early appearance of ELC may imply the existence of coronary heart disease with or without coronary risk factors.

Leukocytosis in non hematological malignancies--a possible tumor-associated marker.

Leukocytosis (WBC counts 10,000/mm3) was detected in 77 out of 252 patients (30%) with ten different types of nonhematological malignancy (NHM) at the time of diagnosis. A full search including serological and bacteriological screening was performed to exclude other possible causes of leukocytosis. Among the different tumors, carcinomas of the lung and colorectum were the most prevalently associated with leukocytosis. Absolute monocytosis was found in 25% of the patients and absolute eosinophilia in only 4.8%. The leukocytosis was attributed mainly to an increase in the mature polymorphonuclears, suggesting a release mechanism of WBC from storage pools by factors secreted or induced by the tumor. Neither the age nor the sex of the patients affected the incidence or magnitude of leukocytosis. However, the presence of metastases was associated with a significantly higher incidence of leukocytosis (p less than 0.05). The associated leukocytosis may be regarded as a poor prognostic sign, and was associated with a significantly (p less than 0.007) shorter survival time. In contrast, absolute lymphocytosis may have a positive effect on the survival time (p = 0.01). Tumor-associated leukocytosis may be an additional tumor-associated marker, of value in assessing and monitoring patients with NHMs.

Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.

Hyperinsulinaemic hypoglycaemia due to chlorpropamide-induced nesidioblastosis.

A 25 year old woman suffering from recurrent attacks of hypoglycaemia underwent a laparotomy for suspected insulinoma. No tumour was found, but histology showed islet cell hyperplasia and nesidioblastosis. Although these changes have been reported as a cause of hypoglycaemia in infants, they are only rarely the cause of hypoglycaemia in adults; in the present case they were found to be the result of covert sulphonylurea administration. The fact that sulphonylureas can cause nesidioblastosis is not well recognised by either physicians or pathologists and it should be considered before "cryptogenic nesidioblastosis" is deemed the cause of hypoglycaemia in adults.

Massive hemoptysis complicating Behçet's syndrome: the importance of early pulmonary angiography and operation.

A 16-year-old patient with Behçet's syndrome had massive hemoptysis due to a ruptured aneurysm of a segmental artery of the left lung. Emergency left lower lobectomy was performed. The patient is well 12 months after operation. There have been no further episodes of hemoptysis.

Accumulation of lactosyl ceramide in leukocytes of patients with adult Gaucher's disease.

Glycosphingolipids were isolated from the leukocytes of 10 patients with Type I, chronic nonneuronopathic (adult) Gaucher's disease and 12 normal subjects, by silicic acid column chromatography and thin-layer chromatography. Quantitation of the individual glycosyl ceramides was achieved by the determination of hexose and sphingosine content, using colorimetric and fluorometric procedures. Lactosyl ceramide, which is the main glycolipid in leukocytes of normal subjects, was significantly increased in the leukocytes of patients with Gaucher's disease. On the other hand, the amount of glycosyl ceramide, which is the main glycolipid accumulating in the reticuloendothelial cells of patients with Gaucher's disease, was similar in Gaucher and in control leukocytes.

Spherulite crystals in synovial tissue of a patient with recurrent monoarthritis.

Frozen, unstained sections of synovial tissue of a 38-year-old man with recurrent monoarthritis and hyperuricemia were studied. Negatively birefringent crystals in a spherulite form were detected by using a compensated polarized light microscope. It is postulated that in some cases of gout the first stage of crystallization is in the spherulite form.

Serum immunoglobulin changes after accidental splenectomy in adults.

Serum immunoglobulin levels were examined in a group of twelve healthy adults who underwent accidental splenectomy. Depressed mean IgM levels and elevated mean IgA levels were found in these patients as compared with the control group consisting of forty-five healthy, untraumatized volunteers. Immunoglobulin changes may have some relevance for the increased tendency to severe infections which has been noted after splenectomy.

Synergism between zymosan-activated serum and heparin in the induction of polymorphonuclear leukocyte aggregation.

During the course of extracorporeal circulation, leukocyte aggregation is known to occur in some patients. This is attributed to complement activation and release of the chemotactic factor C5a. We investigated the effect of heparin on in vitro complement induced aggregation of polymorphonuclear leukocytes (PMNAGG), since most patients undergo heparinization during the extracorporeal circulation. Our results indicate that sub-aggregating concentrations of zymosan-activated serum (ZAS) enhance heparin-induced PMNAGG and that sub-aggregating amounts of heparin increase the aggregation induced by ZAS. Heat inactivation of the serum prior to zymosan activation abrogated the aggregating activity of the ZAS. Furthermore, the combined ZAS and heparin-induced PMNAGG was partially inhibited by specific antibodies to C5a but not to C3a. Therefore, we suggest that heparin and C5a may have a synergistic effect on the aggregation of polymorphonuclear leukocytes. These data might be relevant to situations in which patients are subjected to extracorporeal circulation.

The outcome of bacterial infection in subjects with benign familial leukopenia (BFL).

Benign familial leukopenia (BFL) is a hereditary phenomenon, encountered in several ethnic groups. Subjects bearing BFL are believed to be affected by bacterial infection in no greater incidence than normal subjects. In our study we investigated a group of subjects with BFL during an acute bacterial infection in comparison to subjects without BFL with the same infection. We found that the subjects with BFL had no absolute leukocytosis during the infection. Nevertheless, they reacted similarly to the other subjects in regard to their temperature and heart rate; however, they were hospitalized for fewer days than subjects without BFL. We conclude that BFL is a benign phenomenon, requiring neither specific treatment as such, nor more aggressive therapy during infection. The benign course of an acute bacterial infection in BFL indicates that perhaps the number of WBC's that are normally recruited during an infection in normal subjects highly exceeds that which is necessary.