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Biomedical subjects

S A Weitzman

Publications and source records attributed to S A Weitzman.

At least 91 records · Page 5Linked to original sources
PubMed1983

Overwhelming post-splenectomy infection in Hodgkin's disease: pathogenesis and prevention.

After staging splenectomy, the risk of overwhelming sepsis in patients with Hodgkin's disease reaches 21% in certain subgroups. Youth, recent splenectomy and vigorous chemoradiotherapy predispose patients to this complication. Because of its explosive course and its known microbiology, post-splenectomy sepsis is better suited to prevention than to treatment. Since immunisation prior to treatment produces good antibody responses, all patients with Hodgkin's disease should probably be vaccinated against encapsulated bacteria at least 10 days prior to the onset of therapy.

Adolescent↗
PubMed1983

Cisplatin-vincristine-bleomycin therapy in squamous cell carcinoma of the head and neck.

Seventy patients with squamous cell carcinoma of the head and neck were treated with a 24-hour infusion of cisplatin, followed by vincristine and bleomycin. Among 37 patients with no prior treatment who had stage III (2) or stage IV (35) disease, there were 2 complete responders and 23 with a partial response, for an overall response frequency of 67%. Among 27 patients with recurrent disease after radiotherapy and/or surgery, there were 9 (33%) partial responses. Among 6 patients having failed prior chemotherapy, there was 1 complete responder, still in remission at 26 months. Response frequency was highly dependent on performance status and stage of disease, with a response of 80% in the 0 performance status group and 83% for stages less than T4N3M0. Among 18 patients with resectable disease, 51% remain disease-free at 12 months with an overall median survival at 16 months. Among the 33 patients with recurrent disease, the median duration of response and survival was 4 and 12 months for responders, respectively; nonresponders had a median survival of 5 months. The toxicity of this regimen was generally mild, with 21% of patients having no vomiting and 91% never having a serum creatinine over 2.0 mg/dL. There were 2 cases of pulmonary fibrosis. This chemotherapy regimen compares favorably with other published regimens for head and neck cancer with respect to activity and may be less toxic.

Adult↗
PubMed1982

Comparison of filtration leukapheresis and centrifugation leukapheresis in treatment of lymphosarcoma cell leukemia.

A patient with lymphosarcoma cell leukemia resistant to chemotherapy was treated with filtration leukapheresis and centrifugation leukapheresis. Filtration leukapheresis removed only 10(11) leukemia cells per 8.5 liters of blood processed, while centrifugation leukapheresis removed approximately six times as many leukemia cells from the same amount of blood. Lymph nodes and spleen diminished in size and the WBC count decreased after nine treatments. However, the patient remained markedly thrombocytopenic, and his bone marrow remained infiltrated with lymphosarcoma cells on repeat biopsy. This study shows that centrifugation leukapheresis is superior to filtration leukapheresis in removing significant numbers of circulating lymphosarcoma cells, though the clinical benefit of leukapheresis in this situation remains to be determined.

Blood↗
PubMed1982

Lymphoma with autoimmune neutropenia and hepatic sinusoidal infiltration: a syndrome.

A relation between lymphoma and autoimmune neutropenia, unlike autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, has not previously been well documented. We report a patient with a disorder presenting as autoimmune agranulocytosis, splenomegaly, and infiltration of the hepatic sinusoids by lymphocytes. Antineutrophil antibodies were present. Over a 2 1/2-year period, the illness progressed to an aggressive, poorly differentiated lymphocytic lymphoma with terminal liver failure and fibrosis. Peripheral blood lymphocyte markers identified the tumor as a proliferation of T-cells of the helper class. A review of previous literature disclosed other reports of similar patients who had neutropenia, a lymphoproliferative illness, and hepatic disease. Our case is representative of a previously unrecognized syndrome characterized by autoimmune neutropenia in the setting of a lymphoproliferative disorder of T cells, with a predilection for liver involvement.

Agranulocytosis↗
PubMed1982

Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis.

Phagocytic leukocytes from normal humans can produce mutations in bacteria. To define further the role of oxygen radicals in this mutagenic process, we performed experiments in which scavengers or antioxidants were added to the incubation of phagocytes and bacteria. We found that 1) superoxide dismutase, catalase, mannitol, and benzoate were all capable of inhibiting mutation, 2) sulfhydryl compounds and vitamin E were also inhibitory, and 3) the presence of vitamin C in the incubations increased the mutation frequency. These data suggest an important role for hydroxyl radicals in mediating phagocyte-induced mutations.

Acetylcysteine↗
PubMed1981

Neutropenia after penicillins: toxic or immune-mediated?

Eight patients treated with a total of 220-550 million U penicillin-G developed neutropenia. These cases have been compared with eight patients receiving a similar dose of pencillin-G with no adverse reactions and with eight untreated subjects. All penicillin-treated patients showed raised levels of anti-IgG antibodies and lymphocyte culture stimulation indices. These values were highest in the neutropenia group. Both of the two tests significantly discriminated the three groups. Antineutrophil antibodies could be detected in four of seven neutropenic patients with a staphylococcal-slide-assay while indirect immunofluorescence and microcytotoxicity tests failed to reveal these antibodies. The literature dealing with neutropenias induced by penicillin-G and its congeners is reviewed. We conclude that (1) penicillin-G in doses exceeding a total of 200 million U frequently induces neutropenia, (2) an immune-mediated pathogenesis a highly probable, (3) neutropenia after penicillins is different from two hither-to accepted types of this side effect, (4) sufficiently high amounts of penicillin-G intravenously always induce sensitization against this drug.

Adolescent↗
PubMed1981

Mutation caused by human phagocytes.

Histidine-requiring mutants of Salmonella typhimurium TA100 were incubated with human peripheral blood leukocytes. More of these bacteria reverted to histidine independence than controls not incubated with cells. Phagocyte-rich suspensions were mutagenic, while heat-killed cells, lymphocytes, or mixed blood leukocytes of a patient with chronic granulomatous disease were not. Production of reactive oxygen metabolites could explain the capacity of phagocytes to induce mutation.

Granulomatous Disease, Chronic↗
PubMed1980

Correlation between serum IgG-2 concentrations and the antibody response to bacterial polysaccharide antigens.

We measured serum concentrations of immunoglobulin classes and IgG subclasses in 53 patients who had completed treatment for Hodgkin's disease and in 10 healthy adults. We wished to determine the relation of these classes and subclasses to the subjects' antibody responses to bacterial polysaccharide and viral protein antigens. Mean levels of the IgG-2 subclass were significantly lower in patients treated with both radiation and chemotherapy than in controls (P less than 0.05). The level of IgG-2 before immunization correlated directly with the mean antibody response both to 11 pneumococcal antigens (r = 0.71, P less than 0.001) and to the Haemophilus influenzae Type b antigen (r = 0.40, P less than 0.01). The correlation between IgG-2 concentration and pneumococcal antibody response was also significant in the 10 healthy adults ( r = 0.70, P less than 0.05). The levels of no immunoglobulin class or subclass correlated significantly with antibody responses to influenza A/Victoria/75 and A/New Jersey/76 hemagglutinins, both of which are protein antigens. The serum concentration of IgG-2 appears to provide a marker for predicting the ability to produce antibodies to polysaccharide, but not viral protein, antigens.

Adult↗
PubMed1980

A staphylococcal slide test for detection of antineutrophil antibodies.

We describe a simple test for direct or indrect detection of antineutrophil antibodies. Sensitized leukocytes adherent to glass slides and fixed with paraformaldehyde can be stored in buffer for at least 3 wk. Killed Cowan I staphylococci, containing protein A, bind to sensitized but not control cells, and binding is ascertainable by light microscopy. Indirect tests were positive for 39/41 patients suspected of having immune neutropenia and found to have antineutrophil antibodies by an indirect radiochemical opsonic method. Fifty-four control sera from healthy persons, patients with bone marrow failure, or with immune complex diseases without neutropenia, gave negative indirect tests. Direct tests for cell-bound antibody could be done even during severe neutropenia by reacting fixed autologous cells with staphylococci in the absence of added serum. In some patients only the direct test was positive.

Autoantibodies↗
PubMed1979

5-drug adjuvant chemotherapy for breast cancer.

A series of 41 patients at the MGH who received 5-drug chemotherapy, cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisone, (CMF VP) as adjuvant to surgical treatment of operable breast cancer with 4 or more positive axillary nodes is compared to an analogous group of patients treated with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) reported by Bonadonna et al. in an effort to assess the contribution of the treatment program to disease control. The MGH pattern of disease free survival closely parallels that of Bonadonna. Median disease-free survival among the 24 patients who have not recurred is 27 months; among those who recurred 18 months. The analogous medians for treated patients in the Bonadonna study are 24 months and 16 months, as compared to 27 months and 8 months for his nontreated controls. The treatment program, carried out over a two year period, was well tolerated with excellent patient compliance. There was no significant impact, however, in the disease-free survival of postmenopausal patients. While use of this regimen improved disease-free survival in premenopausal individuals, it is clear that a great deal of room for improvement exists, and newer regimens should be investigated.

Antineoplastic Agents↗
PubMed1979

Antigenic modulation and turnover in human neutrophils.

Turnover of membrane constituents appears important in many biologic processes. We studied this process in neutrophils by immunologic methods. The capacity of neutrophils to recognize other neutrophils coated with antibodies against membrane antigens was used to determine the changes that occur after attachment of the antibody to the neutrophil membrane. Neutrophils were sensitized for 30 min at 22 degrees C with antibodies from three patients with antineutrophil autoantibodies. The sensitized neutrophils were recognized by normal neutrophils, which responded with an increase in glucose oxidation. If, after sensitization, the sensitized neutrophils were not immediately exposed to normal neutrophils, but instead were incubated at 37 degrees C for varying times, the capacity to elicit a recognition response decayed and was gone by 30 min. Additionally, the capacity of the cells to be resensitized by reexposure to antibody also decayed during this period. However, after further incubation at 37 degrees C, the neutrophils recovered the capacity to become sensitized; and this recovery was not inhibited by the addition of cycloheximide. Control incubations with normal immunoglobulin (Ig)G did not elicit a recognition response. The decay in recognition response was temperature dependent. Direct immunofluorescent studies with fluorescein-conjugated antineutrophil IgG revealed that the antibodies were cleared by aggregation and endocytosis. We conclude that: (a) neutrophils clear antibody from the cell surface by a temperature-dependent mechanism; (b) antigenicity is cleared concomitantly; (c) the mechanism of clearance involves internalization; and (d) with time, antigenicity reappears on the cell surface.

Antibodies↗
PubMed1978

Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease.

To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt.

Adolescent↗
PubMed1978

Drug-induced immunological neutropenia.

Antineutrophil antibody capable of opsonising normal neutrophils was detected in the sera of 16 neutropenic patients receiving various drugs. A single drug was involved in 10 cases, multiple medication in 6. 4 patients received semisynthetic penicillins, 8 some form of antimicrobial, and 2 antithyroid agents. Neutrophil counts rose, and antineutrophil antibody activity declined or disappeared, after drug therapy was stopped. Opsonisation related to the semisynthetic penicillins was independent of complement but dependent on drug concentration. Complement-dependent opsonic activity was demonstrated in 2 patients (1 receiving methimazole and 1 receiving multiple medication) and in the patient receiving methimazole this activity was shown to reside in the IgM serum-fraction. In another patient receiving multiple drugs, a complement-independent IgG antibody was demonstrated.

Adolescent↗
PubMed1978

Circulating immune complexes in Hodgkin's disease.

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 microgram/ml +/- 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (less than 15 microgram/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.

Antigen-Antibody Complex↗
PubMed1977

Binding of soluble immune complexes in serum of patients with Hodgkin's disease to tissue cultures derived from the tumor.

We examined 90 serums from patients with Hodgkin's disease for immune complexes and for reactivity with established monolayer tissue cultures prepared from the tumor. All 23 serums with immune complex levels greater than 20 microgram per milliliter were found to react with cultured cells of patients with Hodgkin's disease when tested with antiserums against immunoglobulin heavy and light chains and the C3 component of complement. Five of 11 serums with borderline elevations of immune complexes (10 to 20 microgram per milliliter) and only four of 56 with levels less than 10 microgram per milliliter reacted. Absorption of patients' serums with cultured cells removed immune complexes and eliminated binding to monolayers. Immune-complex-containing serums from 19 control patients did react with cultured cells of patients with Hodgkin's disease; none of serums reacted with normal cultured spleen. Antibodies within complement-containing immune complexes in serums of patients with Hodgkin's disease react with an antigen on the surface of cultured cells of such patients.

Animals↗
PubMed1977

Impaired humoral immunity in treated Hodgkin's disease.

To define the contribution of aggressive lymphoma treatment to the risk of post-splenectomy septicemia, we investigated the humoral immunity of 44 patients with Hodgkin's disease. Specific antibody against Haemophilus influenzae Type b was significantly reduced (mean, 147 ng per milliliter, P less than 0.01) in patients receiving combined treatment (radiotherapy and chemotherapy), whereas single treatment reduced titers marginally (chemotherapy) or not at all (radiotherapy). Untreated patients had normal values (396 ng per milliliter), and splenectomy was without effect. In some patients who received combined treatment, titers were reduced to levels seen in infants. IgM levels were likewise normal in untreated patients. Chemotherapy, however, significantly reduced IgM levels (P less than 0.025), an effect potentiated by prior splenectomy. IgG, IgA, alternate-pathway activity, C3, C4 and CH50 were all normal or elevated. Aggressive treatment with chemotherapy and radiation impairs humoral defense against encapsulated micro-organisms, and thus magnifies the risk of post-splenectomy septicemia in patients with Hodgkin's disease.

Adolescent↗