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Biomedical subjects

H C Lane

Publications and source records attributed to H C Lane.

At least 145 records · Page 8Linked to original sources
PubMed1988

Marked disparity in incidence of bacterial infections in patients with the acquired immunodeficiency syndrome receiving interleukin-2 or interferon-gamma.

STUDY OBJECTIVE: To compare the infectious complications that occurred during trials of immunomodulatory agents in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A survey of two cohorts of patients with AIDS who participated in nonrandomized, unblinded, non-placebo-controlled investigations of the toxicity and efficacy of interleukin-2 and interferon-gamma. SETTING: Clinical research unit in a tertiary care center. PATIENTS: Consecutive samples of 52 patients given interleukin-2 and 22 patients given interferon-gamma. Selection criteria for referred patients included a diagnosis of AIDS, hemoglobin level of greater than 100 g/L (2.0 mg/dL), creatinine level of less than 176.8 mumol/L, bilirubin level of less than 25.65 mumol/L (1.5 mg/dL), the absence of active infection, and the absence of other drug therapy for 2 weeks before entry. Four patients given interleukin-2 failed to complete the study. INTERVENTIONS: Intravenous infusion of natural-product or recombinant human interleukin-2, 250 to 10,000,000 U/day for 23.4 +/- 1.5 (SE) days, or recombinant human interferon-gamma, 0.001 to 1.0 mg/m2.d for 17.7 +/- 4.8 days. MEASUREMENTS AND MAIN RESULTS: Twenty nonopportunistic bacterial infections occurred in 17 of 52 patients given interleukin-2, whereas non occurred in 22 patients given interferon-gamma (P less than 0.05). Bacteremia accounted for 12 of the infections. Staphylococcus aureus and gram-negative bacilli accounted for 16 of the isolates. Opportunistic infections occurred in 6 patients during interleukin-2 infusion and in 1 patient during interferon-gamma infusion (P greater than 0.5). Clinical and immunologic variables and methods of management of intravenous catheters were similar in the two groups. CONCLUSIONS: A marked disparity in infection with nonopportunistic bacteria, but not with opportunistic organisms, occurred in patients with AIDS who were treated with interleukin-2 as compared with those who were treated with interferon-gamma. A high incidence of bacteremia and localized bacterial infection should be anticipated in patients with AIDS who receive interleukin-2.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Etiology and response to therapy.

STUDY OBJECTIVE: To determine the frequency of pathogenic gastrointestinal microorganisms in patients with the acquired immunodeficiency syndrome (AIDS) and diarrhea, and to determine if treatment for identifiable microorganisms improves symptoms. DESIGN: Prospective, consecutive sample study. SETTING: Referral-based clinic and wards, National Institutes of Health. PATIENTS: Twenty of twenty-two consecutive homosexual males with AIDS and diarrhea, and 10 homosexual males with AIDS without diarrhea. INTERVENTIONS: All patients had a complete physical examination; serial stool examinations for viral, bacterial, fungal, and protozoan pathogens; and esophagogastroduodenoscopy and colonoscopy to obtain duodenal fluid and mucosal tissue to analyze for enteric pathogens or histopathology. Patients with diarrhea had a malabsorption evaluation. Patients with treatable pathogenic microorganisms received standard antimicrobial therapy. MEASUREMENTS AND MAIN RESULTS: The 20 patients with AIDS and diarrhea had greater weight loss, lower mean numbers of helper-inducer (OKT4) lymphocytes, and a higher incidence of extraintestinal opportunistic infections than the 10 patients without diarrhea. One or more enteric pathogen was identified in 17 of 20 patients (85%; 95% confidence interval [CI], 65% to 96%) with diarrhea. Only 1 patient without diarrhea was infected with an enteric pathogen. Nineteen of twenty patients with diarrhea and all 10 patients without diarrhea had chronic inflammatory changes in their intestinal biopsy specimens. Sixteen patients with identifiable enteric pathogens and diarrhea were treated; 11 (69%; 95% CI, 43% to 87%) showed microbiologic, histologic, or clinical improvement. CONCLUSIONS: Thorough diagnostic evaluation can lead to the identification of enteric pathogens in a high percentage of patients with AIDS and diarrhea. Specific therapy can lead to symptomatic improvement.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Anemia and erythropoiesis in patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with zidovudine.

We evaluated the development of anemia as part of a trial of zidovudine therapy in patients with the acquired immunodeficiency syndrome (AIDS) with Kaposi sarcoma. Patients were randomized to one of three treatment groups or a placebo group. Transfusion-requiring anemia (hemoglobin less than 100 g/L) developed in 6 of 15 patients on zidovudine therapy at a mean of 6 weeks after starting treatment. A fall in the reticulocyte count was the earliest peripheral blood indicator of toxicity. Mean corpuscular volume increased markedly in patients on zidovudine therapy not developing anemia yet remained stable or only slightly increased in those who became anemic. Bone marrow examination showed pure red cell aplasia in 2 patients, erythroid maturation arrest in 1, and erythroid hypoplasia in 3. Megaloblastic erythropoiesis was present in 2 of the 6 anemic patients. Erythropoietin levels measured at the time of first transfusion were increased. Thus, the anemia associated with zidovudine therapy is due to red cell hypoplasia or aplasia.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV-infected T cells.

The causative agent of the acquired immunodeficiency syndrome (AIDS) has been shown to be a human retrovirus called human T lymphotropic virus (HTLV)-III or lymphadenopathy-associated virus (LAV). The nature of the protective immune response against this virus is currently unknown. We report here results using an antibody-dependent cellular cytotoxicity (ADCC) assay which has been developed for measuring a specific immune response against HTLV-III/LAV. Forty-four sera were examined for their ability to mediate ADCC against HTLV-III/LAV-infected T cells. Sera from healthy HTLV-III/LAV seropositive individuals in the presence of mononuclear cells from healthy HTLV-III/LAV seronegative donors exhibited significantly higher levels of ADCC activity compared to sera from patients with AIDS. Western blot analysis of serum samples indicated that antibody reactivity with the p24 protein of HTLV-III/LAV correlated with higher levels of ADCC activity than did reactivity with Gp120/160. The observation that sera from healthy HTLV-III/LAV seropositive individuals mediated higher levels of ADCC activity than did sera obtained from subjects with AIDS suggests that ADCC may represent a protective immune response to infection with HTLV-III/LAV.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Combination chemotherapy of disseminated Kaposi's sarcoma in patients with the acquired immune deficiency syndrome.

Two clinical trials were conducted to assess the efficacy and safety of a combination chemotherapy regimen for the treatment of Kaposi's sarcoma in patients with the acquired immune deficiency syndrome (AIDS). Eighteen consecutive patients with disseminated Kaposi's sarcoma were treated with a six-drug regimen of doxorubicin (Adriamycin), vinblastine, bleomycin/actinomycin D, vincristine, dacarbazine (ABV/ADV). A brief partial or complete response was achieved in 13 patients. Most patients died of opportunistic infections. Eighteen consecutive patients with disseminated Kaposi's sarcoma were then randomly assigned to therapy with either recombinant alpha interferon or ABV/ADV. The treatment responses in these two groups were comparable to results of earlier trials, and the incidence of opportunistic infections during therapy did not differ between the two treatment arms. It is concluded that chemotherapy is effective and safe for use in palliative management of Kaposi's sarcoma in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Peripheral T cell lymphoma presenting as hypereosinophilia with vasculitis. Clinical, pathologic, and immunologic features.

Peripheral T cell lymphoma developed in two patients several years after an initial clinical presentation of eosinophilia, pruritic skin rash, and vasculitis with lymphocytic infiltrates. Despite treatment with combination chemotherapy, the patients survived less than six months after the malignant lymphoma emerged. Immunologic characterization of tumor cells demonstrated features characteristic of peripheral T cell lymphoma. T lymphocytes from one patient had the uncommon phenotype of T3-negative, T4-positive, T8-negative. Extensive functional studies of this patient's lymphocytes revealed a poor proliferative response as well as an inability to help in immunoglobulin production, despite the preponderance of T4 lymphocytes. It is hypothesized that this syndrome is a consequence of the activity of products elaborated by neoplastic T cells.

Adult↗
PubMed1987

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation.

The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cardiovascular effects and safety of intravenous and intramuscular pentamidine isethionate.

Intramuscular (im) pentamidine isethionate can cause substantial local pain and inflammation at the injection site. This drug is being used more frequently in recent years to treat Pneumocystis pneumonia, particularly in patients with acquired immunodeficiency syndrome. Clinicians began administering it iv despite warnings that iv administration might cause severe hypotension. We investigated the safety of im and iv pentamidine, monitoring hemodynamics after each dose in 11 patients with intra-arterial lines. Results showed only a small (but statistically significant) fall in mean arterial pressure after both im and slow (60 min) iv administration. A concomitant decrease in pulse occurred, but no change in cardiac output, pulmonary capillary occlusion pressure or systemic vascular resistance was noted. These results suggest that it may be safe to infuse pentamidine slowly intravenously. This route is more comfortable to patients than im administration.

Amidines↗
PubMed1987

Prognostic factors and life expectancy of patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

To assess determinants of prognosis for 43 patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia, objective clinical and histopathologic characteristics were analyzed for acute and long-term prognostic significance. Severe abnormalities on initial chest radiographs and alveolar-arterial oxygen differences (AaPO2) greater than 30 mm Hg were associated with higher mortality during the period of treatment for the acute episode (p less than 0.05). Decreased long-term survival after the diagnosis of Pneumocystis pneumonia correlated with the severity of interstitial edema (a component of diffuse alveolar damage) on initial transbronchial biopsy and elevation of AaPO2 at the time of diagnosis (Cox proportional hazards analysis, p less than 0.05). The persistence of Pneumocystis cysts after 3 wk of therapy was associated with significantly decreased long-term survival (p less than 0.05) when follow-up biopsy was performed in 27 of the patients. Patients with a diagnosis of Pneumocystis pneumonia before July 1985 had more advanced disease at the time of diagnosis and a worse prognosis than did those in whom the diagnosis was made after July 1985 (p less than 0.05). This study demonstrates that important prognostic information can be derived from information obtained at initial presentation and follow-up bronchoscopic evaluation in patients with AIDS and Pneumocystis carinii pneumonia, and suggests that early detection and initiation of therapy may improve chances for survival.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunologic approaches to the therapy of auto-immune salivary gland disease.

A variety of immunologic mechanisms may theoretically give rise to disease in the salivary glands. Among them are abnormal antibody production, hyper-reactive T-lymphocytes, and mono- or oligoclonal expansions of B-lymphocytes. While it is not clear which, if any, of these mechanisms are of prime importance in the immunopathology of salivary gland disease, they provide a framework within which to discuss theoretical approaches to the treatment of auto-immune salivary gland disease. Among the techniques used to decrease antibody-induced damage are non-steroidal anti-inflammatory agents, plasmapheresis, and corticosteroids. Cyclosporin, monoclonal antibodies, and biologic response-modifiers may be used to modulate T-cell function, and anti-idiotype antibodies or immunosuppressive agents may be used to treat malignant expansions of B-cells. Although the generally benign nature of auto-immune salivary gland disease precludes the use of many of the potentially toxic treatment regimens discussed here, the appreciation of these approaches to immunomodulation provides a basis upon which to develop new and innovative therapeutic strategies.

Adrenal Cortex Hormones↗
PubMed1987

Nonspecific interstitial pneumonitis in patients with AIDS: radiologic features.

Chest radiographic abnormalities in patients with AIDS usually are associated with opportunistic infection or neoplasm. One hundred five patients with AIDS and clinical evidence of pneumonitis had chest radiographs and underwent bronchoscopy with bronchoalveolar lavage, transbronchial biopsy, or open-lung biopsy. Chest radiographs were abnormal in 73 (70%). Pneumocystis carinii pneumonia was identified at bronchoscopy or open-lung biopsy in 52 (50%). Nonspecific interstitial pneumonitis occurring in the absence of an identifiable infection was documented histologically in 36 (34%). Twenty (56%) of these 36 patients had abnormal chest radiographs. No currently recognized infectious agents were recovered from lavage fluid or were seen histopathologically in patients with nonspecific interstitial pneumonitis. The results show that nonspecific interstitial pneumonitis is clinically and radiologically indistinguishable from Pneumocystis carinii pneumonitis and should be considered in the differential diagnosis of AIDS patients with interstitial infiltrates.

Acquired Immunodeficiency Syndrome↗
PubMed1987

NIH conference. Immunomodulators in clinical medicine.

A major difficulty limiting the use of immunomodulators in clinical medicine has been the complexity of the immunoregulatory network in which modulation of one component usually perturbs the entire system, thus diminishing the specificity of the approach. Lymphokine-activated killer cells infused with interleukin-2 have proved effective in inducing remissions in several advanced cancers, particularly metastatic renal cell carcinomas. The interferons have shown direct antiproliferative effects as well as specific effects on immune function. Alpha-interferon has shown impressive antitumor effects in hairy cell leukemia and significant antiviral effects in papillomavirus infection of the genital tract. Interleukin-2 has multifaceted effects on various limbs of the inflammatory and immune responses and may be the critical common denominator in the adjuvant effects of several other compounds. Monoclonal antibodies have assumed an increasing role in diagnostic and therapeutic approaches to neoplastic and immune-mediated diseases. Finally, several immunomodulators are currently being tested in the treatment of the immune defect of the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Nonspecific interstitial pneumonitis: a common cause of pulmonary disease in the acquired immunodeficiency syndrome.

During a 4.4-year period, nonspecific interstitial pneumonitis was seen in 41 of 110 (38%) patients with the acquired immunodeficiency syndrome and accounted for 32% (48/152) of all episodes of clinical pneumonitis. Diffuse alveolar damage was typically a feature of nonspecific interstitial pneumonitis, but neither lung biopsy nor bronchoalveolar lavage detected a pathogen. Of these 41 patients, 13 had no associated pulmonary tumor and had not been exposed to pulmonary toxins, whereas 28 patients had either concurrent pulmonary Kaposi sarcoma, previous experimental therapies, or a history of pneumocystis pneumonia or drug abuse. Of these 41, 23 had normal chest radiographs. The clinical features of patients with nonspecific interstitial pneumonitis were similar to those of patients with pneumocystis pneumonia, although histologic findings showed less severe alveolar damage in patients with nonspecific interstitial pneumonitis (p less than 0.001). Pathologic evaluation and clinical follow-up suggest that many clinical episodes of pneumonitis in patients with the acquired immunodeficiency syndrome are due to nonspecific interstitial pneumonitis of unknown cause.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Detection of human immunodeficiency virus core protein in plasma by enzyme immunoassay. Association of antigenemia with symptomatic disease and T-helper cell depletion.

A sensitive enzyme immunoassay was developed for detecting human immunodeficiency virus (HIV) core antigen. Assay sensitivity was 3.67 pmol/L of purified HIV core protein, and 1 or 100 in-vitro infectious units/mL of HIV in purified virus preparations or cell culture supernatants, respectively. Enzyme immunoassay sensitivity exceeded that of reverse transcriptase assay by 1000-fold. Core antigen was detected in whole plasma from 41% of symptomatic subjects and 13% of asymptomatic subjects seropositive for HIV. After plasma fractionation, antigenemia was found in 60% of symptomatic subjects and in 33% of asymptomatic subjects seropositive for HIV. Fifty-seven percent of samples from which HIV could be isolated in lymphocyte culture had detectable quantities of core antigen in plasma. However, at least 87% of samples with measurable antigen in plasma had HIV isolated from lymphocyte cultures. Antigenemia was associated with reduced T-cell number and symptomatic disease, and may be a useful marker for disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus.

When B lymphocytes from normal human peripheral blood were incubated for 1 hour with the retrovirus that causes the acquired immune deficiency syndrome (AIDS), the B cells showed marked proliferation and differentiation. Proliferative responses to the virus peaked on day 4 and appeared to be independent of accessory cells. This finding was repeated with three separate viral isolates, one of which was from a patient from Zaire. The magnitude of the observed responses was comparable to that seen with standard polyclonal B-cell activators. This phenomenon may be at least partially responsible for the polyclonal B-cell activation seen in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.

Type beta transforming growth factor (TGF-beta) is a unique polypeptide that has been isolated from a number of different tissues and can induce the phenotypic transformation of non-neoplastic fibroblasts as measured by the stimulation of their growth in soft agar. Recently, TGF-beta has been demonstrated to exert profound inhibitory effects on T and B lymphocyte proliferation. In this study, the effects of TGF-beta on natural killer (NK) cell function were investigated. After 20 hr of culture in the presence of TGF-beta, the NK activity of peripheral blood lymphocytes (PBL) was significantly reduced compared with PBL cultured in medium alone. Similarly, TGF-beta produced a significant depression in the cytolytic activity of highly enriched large granular lymphocytes (LGL). This effect of TGF-beta appeared to be mediated directly on the effector cells, because cultivation of the K562 target cells in TGF-beta did not affect target cell susceptibility to lysis. Binding studies with 125I-TGF-beta indicated that LGL possess approximately 1400 high-affinity (Kd = 1PM) receptors/cell, which represents a considerably higher affinity receptor for TGF-beta than that found on fibroblasts. Culturing of PBL and LGL in TGF-beta resulted in a marked blunting of the boosting of NK cytolysis by interferon-alpha but not by interleukin 2, which suggested that TGF-beta may down-regulate interferon-alpha receptors on NK cells. These results, indicate that in addition to inhibitory effects on T and B cells, TGF-beta also inhibits NK cell function. Although the in vivo role of TGF-beta is presently undefined, it may be an important immunoregulatory protein that has a negative influence on lymphocyte activation.

Cells, Cultured↗