Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We administered one course of 2-chlorodeoxyadenosine (2CdA) at 4 mg/m2 daily for 7 days by continuous intravenous infusion to 46 patients with hairy cell leukemia. Complete remissions occurred in 36 patients (78%; 95% confidence limits, 63% to 89%), partial remissions in five (11%), and a minor response in one. One patient died of candida sepsis 3 weeks after beginning treatment and three patients were clearly resistant to therapy. These three either had morphologically atypical hairy cells, less than 20% of which expressed Ig light chain on the cell surface, or had failed prior treatment with deoxycoformycin and interferon-alpha. At a median of 37 weeks since discontinuation of therapy, recurrent thrombocytopenia has developed in one patient, whose marrow remains normal, while a bone marrow relapse has occurred in another patient, whose blood counts remain normal. Treatment produced a greater than 50% decrease in neutrophil count in 26 patients, which lasted 3 to 4 weeks and was associated with an increased incidence of febrile episodes. These episodes occurred in 21 patients but were associated with documented infection in only four patients. Decreases in the number of CD4+ lymphocytes appeared to occur regularly after treatment and have persisted for a median of 18 weeks without obvious clinical significance. Although years of follow-up will be needed, our results confirm Piro et al's observation (N Engl J Med 322: 1117, 1990) that 2CdA appears to be highly effective in the treatment of hairy cell leukemia.
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PMID:Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA). 134 77

Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. 158 41

Peripheral blood mononuclear cells (PBMC) from patients with severe forms of inherited epidermolysis bullosa (EB) are deficient in functions governing cellular immunity. Very low levels of interferon-gamma (IFN-gamma), interleukin-1 (IL-1), and interleukin-2 (IL-2) were produced in vitro by PBMC from patients with severe forms of EB (recessive dystrophic and dominant dystrophic) as compared to sex- and age-matched controls. Lymphokine production by PBMC from patients with junctional EB was somewhat greater than that from patients with dystrophic forms of EB but was significantly less than that from controls. The production of interferon-alpha was not found to be altered in the severe forms of EB. The PBMC from dystrophic types of EB were also deficient in production of tumor necrosis factors (TNF-alpha and TNF-beta). The degree of the reduction in immune functions was directly related to the severity of skin involvement, with recessive dystrophic EB having the lowest level of cytokine production. This reduced production of monokines and lymphokines may be partially responsible for the progression of cutaneous infections to septicemia and for the metastasis of cutaneous squamous cell carcinomas in patients with severe forms of dystrophic EB.
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PMID:Patients with severe forms of inherited epidermolysis bullosa exhibit decreased lymphokine and monokine production. 212 88

During sepsis or after injection of endotoxin into rats, there is a large increase in muscle protein breakdown and prostaglandin E2 (PEG2) production. Prior studies showed that partially purified interleukin 1 (IL-1) from human monocytes can stimulate these processes when added to isolated rat muscles. The availability of pure recombinant IL-1 and other monokines has allowed us to investigate the identity of the active agent in this process. Incubation of muscles with recombinant human or murine IL-1 alpha or IL-1 beta or with IL-1 plus a phorbol ester did not stimulate muscle proteolysis or PGE2 production. Homogeneous natural porcine IL-1 ("catabolin") and mouse or human IL-1 beta were also not effective in vitro. In addition, a variety of other human cytokines, including tumor necrosis factor ("cachectin"), epidermal thymocyte-activating factor, eosinophil cytotoxicity-enhancing factor, interferon-alpha, beta, and gamma, platelet-derived growth factor, and transforming growth factor (TGF) beta, which are all released by activated macrophages, TGF-alpha, or mixtures of these polypeptides, also failed to activate proteolysis or PGE2 production. By contrast, a large increase in net protein breakdown could be induced in the rat soleus by polypeptides released from porcine monocytes or by the serum from febrile cattle which had been injected with Pasteurella haemolytica or bovine rhinotracheitis virus. Therefore, a still-unidentified product of activated monocytes appears to be responsible for the negative nitrogen balance that accompanies infectious illness.
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PMID:Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines. 328 11

The influence of tumor load, surgical trauma, and bacterial sepsis upon the ability of patient's peripheral leukocytes to produce interferon-alpha (IFN-alpha), the detectable serum IFN levels and circulating serum IFN inactivators were studied. Peripheral blood leukocytes of patients with solid tumors had significantly reduced ability to produce IFN-alpha. Complete resectional surgery resulted in restoration of their ability to produce normal IFN-alpha levels. Circulating IFN levels were detectable in 70% of patients with localized disease while only in 20% of patients with metastatic disease. Interferon-alpha activators were detected in 45% of all patients. Both circulating interferon and IFN-alpha inactivators became undetectable upon tumor resection. Surgical trauma is accompanied by a transient but definite decrease in IFN-alpha production capability. Bacterial sepsis during postoperative days, in patients who successfully recovered, was definitely accompanied by increase in IFN-alpha production capability. Our findings suggest that advanced malignant epithelial tumors have an adverse effect upon the patient's ability to produce interferon and are often accompanied by the presence of circulating serum interferon inactivators. These effects can be reversed by surgical resection of the malignant neoplasm.
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PMID:The effect of malignant epithelial tumors, surgical therapy, and bacterial sepsis upon various parameters of interferon system. 672 84

Bare lymphocyte syndrome (BLS) is a rare disorder characterized by deficient expression of human leukocyte antigens (HLA antigens) and combined immunodeficiency to various degrees. Recurrent severe infections especially due to opportunistic organisms are common. Here, we present two patients with BLS who lack both class I and II antigens (Type III). They had the typical clinical and immunologic findings of BLS. The first patient showed marked improvement in pulmonary symptoms resulting from cytomegalovirus infection by means of gancyclovir treatment. However, intramuscular injections of interferon-alpha (IFN-alpha) had no beneficial effect in either the expression of HLA antigens or the clinical status. The second patient died of septicemia while being prepared for bone marrow transplantation.
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PMID:Bare lymphocyte syndrome with lack of HLA class I and II antigens. Presentation of two cases. 759 64

Interleukin-2 (IL-2) and alpha-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 10(6) U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-alpha-2a at a dose of 6 x 10(6) U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and alpha-interferon does not appear to be better than the single agents used alone in optimal dosage.
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PMID:A phase II trial of concomitant human interleukin-2 and interferon-alpha-2a in patients with disseminated malignant melanoma. 831 96

The ribonucleotide reductase inhibitor, hydroxyurea (HU), augments the cytotoxic effects of 5-fluorouracil (5FU) in vitro; both drugs are synergistic with interferon-alpha (IFN) in vitro. The aim of this phase I study was to determine the maximal duration of HU, 4.3 g/m2, administered as a parenteral infusion in combination with 5FU, 2.6 g/m2 administered over 24 hrs each week, + IFN, 9 MU, subcutaneously three times per week. There were 26 patients enrolled and evaluable. This included 14 patients with colorectal cancer of whom 13 had been previously treated, and 12 patients with other refractory malignancies (pancreas, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and others), of whom 10 were previously untreated. The dose-limiting toxicity of this regimen was myelosuppression. This prohibited dose escalation of HU above the starting dose (24 hrs) on a 6-weeks-on, 2-weeks-off therapy schedule. When filgrastim, 480 microg, was administered subcutaneously on days 3-6, the duration of HU could be extended to 48 hrs on a 2-weeks-on, 1-week-off therapy schedule. There were two instances of fatal infection, one in a patient with a rectovaginal fistula with neutropenic sepsis and the second in a patient with non-neutropenic Clostridium septicum sepsis. All therapy was administered in the ambulatory setting. There were three responders, all among previously untreated patients. High-dose parenteral hydroxyurea, 4.3 g/m2 administered over 24 hrs, can be safely combined with high-dose weekly 5FU, 2.6 g/m2 over 24 hrs + IFN, 9 MU subcutaneously three times per week, without filgrastim in the ambulatory setting. Parenteral hydroxyurea, 4.3 g/m2 over 24 hrs daily x 2 can also be combined with high-dose 5FU + IFN, but requires the addition of filgrastim to avoid severe myelosuppression.
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PMID:Phase I trial of high-dose infusional hydroxyurea, high-dose infusional 5-fluorouracil and recombinant interferon-alpha-2a in patients with advanced malignancies. 882 49

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing immune-mediated neuropathy usually responsive to plasma exchange, intravenous gammaglobulin or steroids, with some patients being refractory to these conventional therapies. We report a patient with CIDP who had spontaneous improvement after an episode of sepsis, but subsequently relapsed with severe generalized weakness; he was unresponsive to the conventional treatments for CIDP but had dramatic improvement following treatment with interferon-alpha 2A. Nerve conduction studies following treatment showed improved distal compound muscle action potential amplitudes without change in the degree of conduction block. The mechanism of action of interferon-alpha is unknown, but it may modulate proinflammatory cytokines that have a role in immune-mediated demyelination. Interferon-alpha may be an effective alternative therapy in patients with CIDP who relapse or are refractory to conventional treatments.
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PMID:Improvement following interferon-alpha 2A in chronic inflammatory demyelinating polyneuropathy. 906 66

Hairy cell leukemia is a rare lymphoproliferative disorder resistant to conventional chemotherapeutic agents. Recently, the purine analogue cladribine (2-chlorodeoxyadenosine, 2-CdA) was introduced for the treatment of this disease. We report on 14 patients with hairy cell leukemia who were treated with 2-CdA at our department between 1993 and 1997. The patients received a single cycle of 2-CdA at a dose of 0.07 or 0.09 mg/kg/day by continuous infusion, over a seven-day period. Five patients were previously untreated, while the others had received prior treatment with interferon-alpha (seven patients), interferon-alpha and splenectomy (one patient) or interferon-alpha, splenectomy and pentostatin (one patient). Six patients achieved complete remission, three a good partial response and three partial remission. Two patients did not respond to treatment and one of them died from septicemia in aplasia. Relapse of the disease occurred in two patients. Side effects such as fever (WHO grade 2) and/or neutropenia (WHO grade 4) were noted in eight patients. Thus, 2-CdA is an effective treatment of hairy cell leukemia that can induce long lasting remissions in both, previously treated and untreated patients.
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PMID:Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine). 1067 89


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