Prospective observations of viral and immunologic abnormalities in homosexual males.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Lange.
Explore the source record for details and available documents.
Vasogenic edema was induced in mongrel cats by cold injury to study uptake and activation of the plasma-kallikrein-kinin system in central nervous system (CNS) tissue. A method was developed for quantitative assessment of kinin formation in affected brain tissue areas. Gross disruption of the blood-brain barrier by focal trauma causes marked penetration of plasma kininogens into necrotic and edematous brain tissue. Moreover, the kallikrein-kinin (KK) system was activated in both necrotic and perifocal edematous areas, and was markedly enhanced by additional cerebral ischemia. Formation of kinins in necrotic brain tissue led to consumption of approximately 60% to 80% of the amount of kininogens being taken up. In perifocal edematous tissue, formation of kinins was less pronounced, or even absent. However, if cerebral ischemia evolved after severe intracranial hypertension, kinins were also formed in the perifocal edematous brain. The intravascular origin of kininogens found in pathological tissue areas secondary to injury was deduced from the observation that cerebral tissue of the contralateral hemisphere with an intact blood-brain barrier had no measurable quantities of kininogens. Consumption of plasma kininogens or formation of kinins were assessed as the difference of the total amount of plasma kininogens taken up into the tissue minus the amount of kininogens found in the brain at postmortem examination. The data indicate that uptake and activation of the plasma-KK system might occur under all pathological conditions in which blood-brain barrier damage permits cerebral penetration of plasma proteins, such as with cerebral contusion, focal ischemia, and tumors. The potent pathophysiological mechanisms induced by kinins in CNS tissue, such as formation of brain edema, microcirculatory dysfunction, and enhancement of blood-brain barrier permeability, together with their formation in focal and perifocal pathological brain tissue, provide further support for a mediator function of the KK system. Methods that specifically interfere with the formation of kinins in damaged brain should therefore be expected to attenuate vasogenic edema.
Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.
The usefulness of bronchoalveolar lavage in the diagnosis of pulmonary infiltrates in the immunosuppressed patient was studied in 97 patients. In immunosuppressed patients, the available diagnostic procedures are often invasive and have variable yield and a potential for serious complications. Bronchoalveolar lavage had an overall diagnostic yield of 66% (61 of 92 diseases). It was most effective in the diagnosis of opportunistic infections, including infection with Pneumocystis carinii (18 of 22 cases), cytomegalovirus pneumonia (10 of 12 cases), fungal pneumonia (5 of 6 cases), and mycobacterial disease (4 of 5 cases). The technique was also helpful in suspected pulmonary hemorrhage (7 of 9 cases) but was less useful for diagnosing malignancy (10 of 22 cases) and drug-induced toxicity (6 of 15 cases). Findings of bronchoalveolar lavage could be combined with those of transbronchial biopsies, brushings, and washings in the diagnosis of most of the diseases. The procedure was safe, even in thrombocytopenic patients and those requiring mechanical ventilatory support. Bronchoalveolar lavage is a valuable procedure for evaluation of pulmonary disease in the immunosuppressed host.
To explore the effect of the acquired immunodeficiency syndrome on gastrointestinal structure and absorption, the cases of 12 homosexual men with the syndrome and 11 homosexual controls were studied. Seven patients had diarrhea with weight loss. Bacterial or parasitic infections were not detected. All patients were malnourished; had significantly fewer T-lymphocyte helper and suppressor cells; and had significantly lower body weights, midarm circumferences, serum albumin concentrations, and iron binding capacities than homosexual controls. D-Xylose malabsorption and steatorrhea were present in patients, especially those with diarrhea. Jejunal and rectal biopsy samples were histologically abnormal in all patients with diarrhea. Jejunal abnormalities included partial villus atrophy with crypt hyperplasia and increased numbers of intraepithelial lymphocytes. Rectal abnormalities included intranuclear viral inclusions, mast cell infiltration in the lamina propria, and focal cell degeneration near the crypt base. The histologic findings suggest that a specific pathologic process occurs in the lamina propria of the small intestine and colon in some patients with the syndrome.
Patients with the acquired immunodeficiency syndrome manifest a wide spectrum of immunologic abnormalities. Polyclonal and antigen-specific differentiation of B lymphocytes into immunoglobulin- and antibody-secreting cells was studied in vitro in three groups of homosexual volunteers: asymptomatic men; men who were symptomatic but lacked clinical criteria for the acquired immunodeficiency syndrome; and those having the syndrome. Although mean responses of all three groups were significantly lower than those of healthy heterosexual male controls, those of the asymptomatic group were least affected. Abnormalities in the symptomatic group were equal to or greater than those of patients with the syndrome, but responses of the latter group were the least augmentable by in vitro manipulations. Severe impairment of B-cell function appeared to favor clinical deterioration. Antibody replenishment might be of value as adjunctive therapy in persons with the acquired immunodeficiency syndrome or as prophylaxis in certain at-risk persons.
Commercial concentrations of radiolabelled lindane emulsion were applied to human skin specimens. Penetration of the substance into the different layers of the skin was examined quantitatively under the common conditions of therapy, but with variation of the period of action (3, 10 and 24 h), condition of skin specimens (intact, stripped), concentration of the emulsion applied (0.3 and 1%) and washing with water only or water and soap after different periods of action (3 and 10 h) and examination at different times after the washing procedure (7 and 14 h). The flux of lindane in the skin was found to be time-dependent. Generally, the concentration increased with the depth of the layer. An increased availability of lindane (in absence of the stratum corneum, and at long application period) resulted in a preferential accumulation in the epidermis and not in the subcutaneous fat. When the intact skin had been washed with soap and water 3 h after application, the concentration of lindane found in the layer below the stratum corneum 7 h later was higher than the one found when the skin had not been washed. When intact skin had been washed after a short penetration period (3 h), this resulted in an introduction of lindane by the washing process. This effect did not occur with stripped skin. Lindane could be more efficiently removed from the stratum corneum with soap and water than with water alone. A threefold increase of the lindane concentration applied resulted in a threefold increase of the concentration in all layers of intact skin specimens. In stripped skin specimens, an increase could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A simple chemical method is described which creates cyanate groups on the saccharide core of bacterial lipopolysaccharide (LPS). The activated LPS molecule is stable at pH 3.5 and can be kept for months at -20 degrees C without loss of properties. The strong reactivity of the cyanate groups permits efficient covalent coupling of various molecules to LPS. This is done under non-denaturing conditions. This paper also describes the coupling of microquantities of antigen (5-10 micrograms) to LPS. The 'LPS-antigen' conjugates are easily purified upon centrifugation at 15,000 X g. These compounds are mitogenic for B cells and trigger in vivo or in vitro production of antibodies directed against the coupled antigen. In vitro, a concentration of conjugate as low as 10(-2) micrograms/ml triggers specific antibody synthesis. Injection of 5 micrograms of conjugate in mice induces a humoral response detectable 7 days after immunization. B cells cultured for 5 days with an adequate dose of the LPS-beta-galactosidase conjugate were fused with the Sp2-0-Ag cell line to give anti-beta-galactosidase hybridomas.
Explore the source record for details and available documents.
A new commercially developed cytomegalovirus (CMV)-IgM ELISA was found to be sensitive and specific when compared with sucrose gradient fractionation of Ig classes in CMV antibody-positive and negative sera. The presence of CMV IgM in patients' sera correlated with positive virus isolation from circulating mononuclear blood cells and urine. Serial examinations of patients with primary or recent CMV infection revealed a typical sequence of IgM and IgG development. The frequency of CMV isolation declined as the concentration of IgM decreased and the IgG levels increased. Since the isolation of CMV from clinical specimens is a cumbersome procedure, we suggest that the IgM ELISA could provide rapid and valuable information on the presence of an active or reactivated CMV infection.
Explore the source record for details and available documents.
Hybridomas secreting monoclonal antibodies directed against Rat gastric L-histidine decarboxylase (H.D.) have been obtained from a partially purified preparation and screened by immunoprecipitation of the enzyme activity. They cross react with Rat brain H.D., indicating at least that these two enzymes share common antigenic determinants.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In a controlled clinical trial, 52 patients with ER positive metastatic breast cancer were randomly assigned to receive initial treatment with either tamoxifen alone followed by sequential cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after tumour progression of concurrent tamoxifen plus CMF, All 52 patients entered are eligible and 50 patients were currently assessable. Response rates (CR + PR) were similar for the two treatment groups (15/24 tamoxifen alone, 17/26 tamoxifen + CMF). The median durations of survival for the two treatment groups 17.7 months and 17.1 months were also not significantly different. Significant correlations were found between level of ER and response rate and also between level of ER and response duration. From the result of this investigation it would appear that there is no advantage to the addition of chemotherapy prior to an adequate trial of hormone therapy in patients with metastatic ER positive breast cancer.
Explore the source record for details and available documents.