PubMed Health⌕ Search

Biomedical subjects

R Medenica

Publications and source records attributed to R Medenica.

At least 19 recordsLinked to original sources
PubMed1997

Cytokine patterns in adults with AIDS.

BACKGROUND: It has been reported that in HIV infected patients enhanced production of IL-4 and IL-10 in response to stimulation of peripheral blood lymphocytes with phytohemagglutinin is associated with disease progression. Some have proposed that a switch from a cytokine profile associated with CD4+ Th1 predominance (IL-2, IFN-G, TNF-B) to Th2 predominance (IL-4, IL-5) plays a major role in the progression of HIV infection. Others find no clear evidence for the dichotomy of Th1 and Th2 predominance in HIV infected patients Discrepant results have been reported in studied populations in which only a few cytokines have been examined. METHODS: Thirty-one adult patients with AIDS but without other active infections provided serum and peripheral blood lymphocytes for determination of cytokine levels. Their responses were compared to those of five normal healthy volunteers without active infection. ELISA techniques were employed to quantitate cytokine levels. Both circulating lymphocyte and enriched lymphocyte populations were studied with and without stimulation employing phytohemagglutinin and/or rhIL-2. RESULTS: Patterns of cytokine expression were analyzed in 31 adult patients with AIDS but without other active infections. All had CD4+ cell counts below 50 and large viral loads (Roche PCR). The unstimulated cytokine profile in these patients generally showed marked elevations in IL-1, IL-3, IL-4, IFN-G, TNF-A, TNF-B, OSM, and TGF-B. Minimal elevations compared to normal healthy volunteers were noted for IL-2, IL-6, IL-8, IL-12, IFN-A, and IL-6SR. The levels of RANTES were lower than in normal healthy volunteers. Responses of peripheral blood lymphocytes to stimulation with phytohemagglutinin showed enhancement of all cytokines in all subjects studied though the response was much less marked in AIDS patients than in normal volunteers with the exception of IL-3, IL-4, IL-8, TNF-B, and TGF-B which are increased. Little difference in IL-2 and IL-12 expression was noted between stimulated peripheral blood lymphocytes of AIDS patients and normal healthy volunteers. No relation was noted with patient age or with any use of antiretroviral agents. Recombinant human IL-2 was a less potent stimulant than was phytohemagglutinin. CONCLUSION: The character of cytokine response in AIDS patients may be directly related to the stimulus employed in test systems. There is no evidence for Th1/Th2 dysregulation. Cytokine elevations in AIDS patients generally are reflective of chronic infection (the virus). Lymphocytes from AIDS patients do not respond as well to stimulation as do those from normal healthy volunteers. The stimulated lymphocyte response in AIDS patients suggests there is underlying low-grade host versus virus reaction in these patients (exaggerated responses of IL-3, IL-4, IL-8, TGF-B).

Acquired Immunodeficiency Syndrome↗
PubMed1997

Polypeptide levels increase during acute onset of hepatic porphyrias.

Hepatic porphyrias are characterized by neurological symptoms manifested by abdominal pain, neuropathies and mental aberrations. Porphyrins are ubiquitous and essential biochemical constituents of living beings acting as mediators of oxidation reaction in the metabolism of the steroid, drugs, environmental chemicals or as a mean of exchanging gases, such as oxygen and carbon dioxide between the environment and the tissue of the body using endogenous polypeptide properties. The different porphyrins arising from the arrangement of normal heme synthesis are characterized by an accumulation and excretion of specific intermediate porphyrins and/or of precursors exerting toxic effect, initiating cascades of generations of polypeptides, neurotransmitters and gut-brain axis peptide responsible for the symptoms of clinical status. We studied polypeptide levels in 27 patients (19 females, 8 males) presenting acute attack of hepatic porphyria: 2 with ALA dehydratase-deficient porphyria; 9 with acute intermittent porphyria; 12 with porphyria cutanea tarda and 4 with variegate porphyria. During acute attacks of porphyria, polypeptides were found to be constantly increased: vasoactive intestinal polypeptide (VIP); neurotensin (NT); substance P; pancreatic polypeptide; gastrin-releasing peptide; gastrin and motilin. Administration of the somatostatin (antagonizing polypeptide), which was undetectable or low before treatment, apparently alleviated the acute symptomatology. Elevated levels of polypeptides, at least partly, contribute to appearance of acute symptoms in porphyria patients.

Acute Disease↗
PubMed1995

Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.

Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.

Adjuvants, Immunologic↗
PubMed1994

Immunomodulation in the treatment of malignant disorders.

In this study, 91 patients with metastatic solid tumor were treated with an immunomodulatory regimen of interferons -a and -g as well as octreide in pulse administration, followed in selected patients by low dose perilymphatic administration of interleukin-2. Pharmacosensitivity studies of patient tumor directed concomitant chemotherapy. High levels of circulating interferon-a (> 50 IU/ml) and the presence of lymphokine inhibitor factor were identified prior to treatment. None of the patients was able to produce autologous interferon. All patients had been previously treated with surgery and/or radiation therapy and/or chemotherapy. Patients had also received second line chemotherapy and/or radiotherapy per current protocols. At 30 days following immunomodulatory therapy, 6/91 patients were in complete remission; 12/91 were in partial remission; six patients progressed. At 180 days, with concomitant stem cell assay directed chemotherapy, 24/91 patients were in complete remission; 36/91 demonstrated a partial remission. Six patients progressed. Responders demonstrated a fall in circulating interferon levels as well as lymphokine inhibitor factor concomitantly with reduction in tumor burden. NK cell activity increased. Marrow studies demonstrated rises in granulocyte and thrombocyte stem cell activity. Macrophage activity also increased. The rationale for the approach is discussed.

Drug Administration Schedule↗
PubMed1985

Clinical results of leukocyte interferon-induced tumor regression in resistant human metastatic cancer resistant to chemotherapy and/or radiotherapy-pulse therapy schedule.

The efficacy of Human 6 IFN (HLIFN) given in a pulse fashion was determined in a phase II study. Ninety-one cancer patients were evaluated (9 myeloma, 12 breast, 14 prostate, 9 melanoma, 4 renal, 6 astrocytoma, 7 ovarian, 9 large bowel, 7 gastric, 14 head and neck). They all had advanced progressive cancer that was resistant to chemotherapy and/or radiotherapy. Patients were treated by intramuscular injection of 6 X 10(2) I.U./m2 for three consecutive days every four weeks. 84 patients were evaluable. Complete clinical response was obtained in 23 patients (4 myeloma, 2 breast, 5 prostate, 1 melanoma, 1 renal, 2 astrocytoma, 2 ovarian, 2 large bowel, 1 gastric, 3 head and neck). Partial responses were observed in 35 patients (3 myeloma, 7 breast, 6 prostate, 4 melanoma, 1 renal, 2 astrocytoma, 3 ovarian, 4 head and neck). Objective responses were related (P less than 0.01) to serum IFN level, with complete and partial responses (P less than 0.01) more commonly seen in those patients whose serum IFN levels at two hours were in the range of 1000 to 1650 I.U./ml. Side effects resulting from pulse IFN were acceptable for this group of patients and consisted of fever, transient chills, malaise and asthenia, and transient thrombocytopenia and leukocytopenia. The extent of fever was directly related (P less than 0.01) to response, and was most elevated in patients who achieved objective responses. IFN administered in a pulse fashion appears to be more effective than daily IFN and merits further evaluation.

Adenocarcinoma↗
PubMed1981

Combined chemotherapy of head and neck squamous cell carcinomas with methotrexate, bleomycin, and hydroxyurea.

Thirty-two patients with squamous cell carcinoma of head and neck not amenable to surgery or radiotherapy were treated with a combination of methotrexate 0.6 mg/kg IV weekly, bleomycin 15 mg IV weekly, and hydroxyurea 1,000 mg/m2 three oral doses weekly. Eleven complete responses and ten partial responses of more than 50% were observed. The mean duration was 43 weeks for complete responses and 35 weeks for partial responses. Toxicity consisted in leukopenia, thrombocytopenia, nausea, vomiting, stomatitis, and cutaneous alterations. Only one patient suffered reversible lung toxicity. These results suggest that a combination of three drugs in squamous cell head and neck cancer may be more effective than a combination of bleomycin and methotrexate only.

Antineoplastic Agents↗
PubMed1978

Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid.

DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in myelosuppression, particularly thrombopenia and skin rashes. At the 3 mg CF level, 18 out of 26 patients developed toxicity. No toxicity was seen at the 30 mg CF level in 11 patients. After cessation of CF, toxicity occurred in five out of seven patients. After the onset of toxicity, CF was added as a delayed rescue, in a dosage of 15 mg every 8 h or 30-60 mg daily. One patient died of sepsis with agranulocytosis. All other patients recovered from myelosuppression within 1 or 2 weeks. Objective responses were observed in seven patients, four of the ten with epidermoid cancer of the head and neck, two out of eight with epidermoid cancer of the lung, and one out of three with melanoma.

Adult↗
PubMed1976

[Granulocyte transfusions. Technical data, granulocyte function and results].

A new method called "repetitive filtration leukopheresis" is described for granulocyte transfusion therapy. 23 patients received a total of 91 transfusions. All patients presented neutropenia of less than 300/mm3 and various kinds of infection resistant to antibiotic therapy. A favorable result was observed in 18 cases following these transfusions, which did not produce the secondary effects noted by others (chills, rash, fever, dyspnea). It was felt that this remarkable tolerance was a result of the collection procedure (elution at pH 7.4 ommission of centrifugation, thus securing the functional integrity of the cells). This impression was confirmed by the results of a battery of tests performed on the collected granulocytes, which included evaluation of their phagocytic and bacteriolytic functions and of their ability to break down a phagocytized antigen, together with measurements of lysosomial enzymes released in the supernatant.

Bacteriolysis↗
PubMed1976

[Treatment of disseminated oro-pharyngo-laryngeal epidermoid carcinomas with a combination of methotrexate and bleomycine in small doses].

In the previously published series of patients with generalized head and neck epidermoid carcinoma, a high dose combination of methotrexate (MTX) (0.4 mg/kg biw. i.v.) and bleomycin (BLM) (30 mg biw. iv) produced an objective remission rate of 60% with a median duration of 9 weeks. The disappointingly short duration of the remissions was tentatively related to the short period of treatment, which was limited to 5 weeks in order to keep the cumulative dosage of BLM below 300 mg. In the present study, covering 26 patients, a lower weekly dose was adopted (BLM 15 mg, MTX 0.6 mg/kg). 13 partial remissions were obtained with a median duration of 26 weeks; in 7 cases there was no evolution, in 6 cases progression of the tumor was registered, and there was one death from hematological toxicity. The major toxicity was leuko- and thrombopenia with one toxic death. Digestive and cutaneous side effects and fever were minor. There were 2 cases of major pulmonary toxicity, one of which was lethal. In conclusion, a combination of MTX and BLM at a relatively low dosage is active in disseminated head and neck carcinoma and appears to be compatible with longer maintenance of palliation in comparison with results obtained at a high dose level.

Bleomycin↗