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Biomedical subjects

R Sabo

Publications and source records attributed to R Sabo.

17 recordsLinked to original sources
PubMed2001

Nasal nitric oxide and the nasal cycle.

OBJECTIVES: To establish the relationship between nasal patency and the nitric oxide (NO) concentration in the nasal airways. METHODS: Unilateral nasal NO concentration (n = 11) and inhaled nasal NO concentration at oropharynx (n = 9) were measured in healthy adult volunteers. Subjects breathed normally through the nose with a known resistance (ranged from none to total occlusion) placed in one nostril. In a subgroup (n = 7), the unilateral nasal NO concentrations were determined with nasal cavity congestion induced by lateral decubitus. RESULTS: When the added nasal resistance was less than 6 cm H(2)0 per liter per second, the peak NO concentrations in the nose remained below 80 parts per billion (ppb). Thereafter, the higher the resistance, the greater the NO concentration. It was up to 1109.7 ppb when the front nostril was totally occluded. There was no correlation between oropharyngeal NO concentrations and resistance in the front of the nose (r = 0.4). There was a significantly negative correlation between nasal cavity volumes and nasal NO concentrations (r = -0.8, P <.001). CONCLUSIONS: Increases in nasal resistance to levels encountered in the nasal cycle and in recumbency augments the NO concentration within the obstructed side of the nose. Although that within the nose changes with patency, the NO concentration is constant down to the lower airways. The modulation role of the upper airways to the inhaled NO concentration remains unclear.

Adult↗
PubMed2001

Metastatic hypernephroma to the head and neck: unusual case reports and review of the literature.

Hypernephroma is one of the most common tumours to spread by extranodal metastases to the head and neck. We herein report on six patients with unusual metastatic hypernephroma to the head and neck area. In two of the six cases, the metastatic tumour in the head and neck was the presenting symptom, and the renal tumour was secondarily detected. Metastatic hypernephroma to the head and neck area has been demonstrated mostly in the paranasal sinuses, parotid gland, and the mandible. Among the six cases presented, four belong to the above-mentioned group, but the other two are rather rare cases, one metastatic to the nasopharynx and soft palate and the other to both lobes of the thyroid gland. Hypernephroma should be sought and excluded whenever a metastatic lesion is encountered in the head and neck area, even if the metastatic lesion is the first clinical presentation. The diagnosis of metastatic hypernephroma should be suspected in any patient with even a remote history of renal cell carcinoma.

Adult↗
PubMed2000

Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.

Adult↗
PubMed2000

A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.

The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.

Adult↗
PubMed2000

Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

Absorption↗
PubMed1999

Effects of single intravenous doses of recombinant human interleukin-10 on subsets of circulating leukocytes in humans.

Recombinant human interleukin-10 (rhIL-10) is a potent and specific immunomodulatory agent which inhibits endotoxin-stimulated pro-inflammatory cytokine production by monocytes, blocks T-lymphocyte activation by antigen presenting cells, and modulates T(H)1/T(H)2 balance in immune responses. In previous clinical trials, rhIL-10 administered to healthy volunteers induced rapid and transient elevations of neutrophil and monocyte counts and reductions of lymphocyte counts in addition to suppression of endotoxin-stimulated whole blood cytokine synthesis. We sought to better characterize the effects of rhIL-10 on immunophenotypically defined subsets of circulating leukocytes that could be relevant to its immunomodulatory effects. Healthy volunteers were given single doses of 10 microg/kg rhIL-10 (n = 8) or equivalent placebo (n = 4) by intravenous injection. Significant changes of circulating leukocytes included transiently increased neutrophils and monocytes with parallel increases of CD33+ and CD14+ cells. Total lymphocytes as well as total CD3+, CD3+/CD4+ and CD3+/CD8+ cells transiently decreased. Mean fluorescence intensity of CD11a (integrin alpha-chain subunit of lymphocyte function antigen-1, LFA-1) on lymphocytes transiently but significantly decreased, suggesting a mechanism for transient alteration of lymphocyte trafficking. In addition, mean fluorescence intensity of HLA-DR (major histocompatibility class II) on CD14+ cells (predominantly monocytes) transiently but significantly decreased, implying a possible alteration of antigen presenting function. Further study will be required to elucidate the immunomodulatory roles and potential clinical significance of these hematologic changes in therapeutic trials of rhIL-10 in patients with chronic inflammatory and autoimmune diseases.

Adult↗
PubMed1998

Reconstruction of the soft palate by uvulopalatal flap.

Surgical removal of the soft palate in cases of neoplastic disease has a functionally detrimental effect on the patient, resulting in rhinolalia and nasal regurgitation. The authors describe their original surgical technique for repairing the lateral soft palate defect using a uvulopalatal flap. The flap is readily available and the procedure is single staged and without sequela. The aim of this reconstructive procedure is to obtain a diminished soft palate defect by primary surgery. In five patients who underwent a partial excision of the soft palate, the surgical defect was corrected at the time of initial surgery by a uvulopalatal flap. In this technique, the surface of the defect was diminished, postoperative rhinolalia and regurgitation were unremarkable, and sometimes an obturator was obviated. Using a local myomucosal flap, the procedure is simple, safe, and effective.

Adult↗
PubMed1998

Oropharyngeal fatty infiltration in obstructive sleep apnea patients: a histologic study.

It has been suggested that due to fatty infiltration, obstructive sleep apnea (OSA) patients have a narrower pharyngeal airway than normal persons. To identify potential fatty infiltration of pharyngeal tissues that may contribute to OSA, a histologic study of the distal soft palate was performed. Histologic sections of 46 oropharyngeal specimens were evaluated. This included 25 overweight OSA patients (25/31), 6 normal-weight OSA patients (6/31), and a control group of 15 healthy (non-OSA) individuals. A semiquantitative analysis of the fatty tissue was performed. In all 31 OSA patients an excess of fatty infiltration was found in the histologic oropharyngeal specimens in comparison to the control group. No correlation was found between the pharyngeal fatty infiltration degree, the body mass index, and the apnea index. Irrespective of their body weight, in none of the patients without OSA was excessive fatty infiltration seen. It is suggested that excessive pharyngeal fatty infiltration plays a role in upper airway obstruction in OSA and that it can be associated with the development of apnea.

Adipose Tissue↗
PubMed1997

Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers.

Interleukin-10 inhibits T-lymphocyte activation and proliferation and lipopolysaccharide-induced monocyte production of proinflammatory cytokines. Fifty-four healthy volunteers received single doses of recombinant human interleukin-10 (1.0, 2.5, 5.0, 10, 25, or 50 micrograms/kg) or placebo by subcutaneous injection (randomized double-blind assignment). Clinical adverse events were infrequent at doses below 50 micrograms/kg (five of six subjects had mild flu-like syndrome). Mean serum interleukin-10 concentrations were dose related. The mean terminal-phase half-life ranged from 2.7 to 4.5 hours, and the apparent volume of distribution ranged from 0.70 to 1.35 L/kg. Hematologic changes included transient mild to moderate increases of neutrophil counts, decreases of lymphocyte counts, and a delayed decrease of platelet counts. Recombinant human interleukin-10 significantly suppressed production of the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha by whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide.

Adult↗
PubMed1997

Activity and tolerance of a continuous subcutaneous infusion of interferon-alpha2b in patients with chronic hepatitis C.

We administered interferon-alpha2b (IFN-alpha2b) by continuous subcutaneous infusion (60,000 IU/h, or 10 million IU/week) over 3 months to 7 patients with chronic hepatitis C. All had previously responded, as assessed by normalization of transaminases to the same dose of IFN administered by intermittent injection over 6 months, but had relapsed after cessation of therapy. The continuous infusion was tolerated well at the site of infusion, and the systemic side effects were similar in type but were lesser in intensity than with intermittent dosage. Four of 7 subjects had normalization of transaminase at the end of week 12 of therapy. Serum HCV RNA and HCV by PCR decreased with treatment, and there was a prompt and sustained increase in serum beta2-microglobulin and of 2', 5' OAS activity. The level of the latter appeared to correlate with response of the transaminase. Serum IFN concentrations were low but detectable throughout therapy. After stopping IFN administration, the transaminases in responders increased again to pretreatment levels.

Administration, Cutaneous↗
PubMed1995

Internal jugular vein patency after functional neck dissection: venous duplex imaging.

We present a retrospective study performed to determine jugular patency after functional neck dissection (FND). Twenty-six patients, 16 females and 10 males, ranging in age from 16 to 78 were examined. These patients underwent either unilateral FND or bilateral FND for cervical lymph node metastases. Cervical duplex and pulsed Doppler imaging were chosen to determine internal jugular vein (IJV) patency. The examination was performed after a minimum postoperative period of 2 months and a maximum one of 22 years. Thirty-one IJVs were examined. All but 4 IJVs examined were found patent postoperatively. The preservation rate of patency of the IJV in FND was found to be high (27 of 31 or 87%). These results favor the use of FND for IJV preservation, particularly in bilateral neck dissection.

Adolescent↗
PubMed1994

[Thyroidal oxyphilic tumors].

Treatment of thyroidal oxyphilic (Hurthle cell) tumors is controversial due to difficulties in grading tumor malignancy. We classify these tumors into 3 histological subtypes: adenomas, atypical adenomas, and carcinomas. The purpose of this study was to find out whether this classification is a useful criterion for determination of the extent of surgery. Our retrospective study included 5 cases of adenoma, 2 of atypical adenoma and 13 of carcinoma. All histological specimens were revised and were stained immunohistochemically for thyroglobulin. All specimens were positive for thyroglobulin; staining for factor VIII was performed in cases in which the tumor had penetrated into blood vessels. Hemithyroidectomy was used for typical adenomas, while atypical adenomas were treated as carcinomas and total thyroidectomy was performed. 5 patients were treated with radioactive iodine. Taking into account the clinical results, we conclude that histological subtype is a useful guide for proper surgical management. Hemithyroidectomy is proper therapy for adenomas. The management of atypical adenomas was not determined as all were treated as carcinomas.

Adenoma↗
PubMed1990

Cervical spinal canal plasticity in children as determined by the vertebral body ratio technique.

The sagittal cervical canal measurement from a plain spine radiography is easy to obtain and has a smaller range than the interpedicular distance. In an effort to standardize the sagittal measurement, a canal ratio, using the vertebral body diameter, has been formulated. If this method is to be used in the pediatric spine, the effect of the growing neuraxis must be considered. Lateral cervical spine radiographs of 301 normal children and adults were evaluated and grouped according to age. The canal ratio measurement demonstrated a consistent decrease through to the adult groups. Adjacent groups showed statistically significant decreases with age in all groups tested other than the oldest two groups. With the pediatric spinal canal vulnerable to various intracanalicular influences, the canal ratio may reflect early disease processes.

Adolescent↗
PubMed1988

Pharmacokinetics of roxithromycin (RU 965).

This report contains the findings of five studies performed to evaluate the pharmacokinetics of roxithromycin (RU 965), a new macrolide antibiotic. Roxithromycin was given as 150- and 300-mg film-coated tablets. The drug is rapidly absorbed after oral administration. Peak plasma levels following 150- and 300-mg doses occur within two hours. Steady state is reached within four days with doses of 150 mg twice a day or 300 mg once daily. The plasma half-life is approximately 12 hours. About 10% of the dose is excreted in urine. Although dose dependency was observed for the various pharmacokinetic parameters, dose proportionality could be demonstrated only in terms of the percentage of the dose excreted in urine. The rate of absorption is not affected by age. The rate of elimination and renal clearance are decreased in healthy elderly subjects, however, these differences should not be clinically meaningful. The bioavailability of the drug is not affected to a clinically meaningful extent when it is given with milk. Less than 0.05% of the administered dose is excreted in the breast milk of lactating women. Roxithromycin was safe and well tolerated with no clinically meaningful changes in any of the safety variables in any of the five studies reported.

Adult↗
PubMed1988

The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men.

Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. Gastric secretions were collected by aspiration using a nasogastric tube placed in the distal part of the stomach. Gastric fluid volume, pH, and acid concentrations were determined for 2 hours before drug administration and over 24 hours after administration on days 1, 7, 14 (the last day of dosing), and 17 (3 days after the last dose). Plasma and urine samples were collected throughout the study for the pharmacokinetic assessment. All subjects completed the study without side effects or clinically significant changes in any of the safety variables. Subjects receiving roxatidine acetate had substantial increases in gastric pH and decreases in acid secretion compared to baseline and to placebo-treated subjects. The duration of effect was approximately 12 hours. Nocturnal pH was greater than or equal to 6.0 in 80% of the roxatidine acetate-treated subjects. When sampled 3 days after the last dose (day 17) no differences in pH, acid secretion, or gastric volume were observed between the roxatidine acetate- and placebo-treated groups. The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and decreases in gastric acid concentration, without affecting gastric fluid volume.

Adult↗
PubMed1984

The pharmacokinetics and bioavailability of nomifensine maleate in healthy men.

Two studies were conducted in normal male volunteers to establish the pharmacokinetic parameters for nomifensine maleate and to determine the bioavailability of the drug from the Merital capsule intended for U.S. marketing. Single oral doses of 25, 100, and 200 mg of nomifensine maleate as aqueous solutions were administered to 24 men in the open-label Latin-square design pharmacokinetic study. In the bioavailability study, 24 men received single oral 50 mg doses of nomifensine maleate in a capsule or as an aqueous solution. Plasma levels of nomifensine were determined by radioimmunoassay and urinary levels of total nomifensine and its metabolites were assayed by thin-layer chromatography. There was a proportional increase in the area under the curve (AUC) with increasing dose, while peak plasma levels and amounts of total nomifensine and its metabolites excreted in the urine rose as dose increased. The pharmacokinetics of nomifensine are considered linear over the dose range tested. Nomifensine maleate was equally bioavailable from the 50 mg aqueous solution and the Merital capsule formulation.

Administration, Oral↗