Specific incremental field test for aerobic fitness in tennis.

OBJECTIVES: To compare metabolic and cardiorespiratory responses between subjects undergoing incremental treadmill (non-specific) and tennis field based (sport specific) tests. METHODS: Nine junior competitive tennis players randomly performed two incremental protocols to exhaustion: a treadmill test (TT) and a tennis specific fitness test (FT). The FT consisted of repeated displacements replicating the game of tennis at increasing speed on a court. In both tests, ventilatory variables and heart rate (HR) were determined at the ventilatory threshold (VT), respiratory compensation point (RCP), and maximal loads (max). Blood lactate concentration was determined at the point of volitional fatigue. RESULTS: Percentage (mean (SD)) maximal HR (83.6 (5.1) v 83.0 (2.8) and 92.1 (2.1) v 92.3 (2.1)%, respectively) and percentage maximal oxygen uptake (VO2max) (69.4 (8.1) v 73.5 (6.1) and 84.4 (6.5) v 85.5 (8.7)%, respectively) at the VT and RCP were not different between the FT and TT subjects, whereas VO2max was higher in the FT than in the TT (63.8 (3.0) v 58.9 (5.3) ml/min/kg; p<0.05). Blood lactate concentration (10.7 (3.0) v 10.6 (4.3) mmol/l) did not differ between the TT and FT. CONCLUSIONS: Although cardiorespiratory variables were not different at submaximal intensities between the two tests, VO2max values derived from laboratory measurements were underestimated. Using field testing in addition to treadmill testing provides a better measurement of a player's individual fitness level and may be routinely used to accurately prescribe appropriate aerobic exercise training.

Combination of magnetic parameters: an efficient way to discriminate soil-contamination sources (south France).

Biplots combining magnetic parameters allow to identification and differentiation different pollutant emission sources. A major problem in soil pollution is the characterization of the relative contributions of different anthropogenic particles sources. This paper demonstrates the efficiency of magnetic techniques to provide identification and differentiation of contaminating emission sources. About 100 soil samples were collected across a mixed agricultural and industrial area (Crau plain/Berre-Fos basin) in southern France. Nine soil profiles were realized. They are aligned along a transect, from the Mediterranean cost to the north. Measurements of initial magnetic susceptibility (chi) and remanent magnetization (ARM, IRM) have been carried out at room temperature. Several ratios of magnetic parameters were calculated and tested. Bivariate analyses allow to characterize different pollution sources and graphic results suggest three dominant contributions originated from road traffic, airport and steel industry. Moreover, magnetic grain-size discrimination between surface-soil samples and bottom-soil samples is obtained. An increase of hard magnetic components from topsoil towards the bottom of the profiles is evidenced.

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation-induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available. METHODS: The safety and efficacy of 0.15% benzydamine oral rinse in preventing or decreasing erythema, ulceration, and pain associated with oral mucositis during RT were evaluated in a randomized, placebo-controlled trial conducted in patients with head and neck carcinoma. Subjects were to rinse with 15 mL for 2 minutes, 4-8 times daily before and during RT, and for 2 weeks after completion of RT; study evaluations were conducted before RT and routinely thereafter up to 3 weeks after RT. RESULTS: During conventional RT, regimens up to cumulative doses of 5000 centigrays (cGy) benzydamine (n = 69) significantly (P = 0.006) reduced erythema and ulceration by approximately 30% compared with the placebo (n = 76); greater than 33% of benzydamine subjects remained ulcer free compared with 18% of placebo subjects (P = 0.037), and benzydamine significantly delayed the use of systemic analgesics compared with placebo (P < 0.05). Benzydamine was not effective in subjects (n = 20) receiving accelerated RT doses (> or = 220 cGy/day). The incidence of adverse events between treatment groups was comparable without significant differences. Early discontinuation because of adverse events occurred in 6% of benzydamine subjects and 5% of placebo subjects, and there was 1 death (related to the primary diagnosis) in a placebo subject. CONCLUSIONS: Benzydamine oral rinse was effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis.

Topical transforming growth factor-beta3 in the prevention or alleviation of chemotherapy-induced oral mucositis in patients with lymphomas or solid tumors.

Transforming growth factor (TGF)-beta3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemotherapy (CT). Two double-blind, placebo-controlled, multicenter, phase II studies of TGF-beta3 were initiated in the United States, Europe, and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-beta3 (25 microg/mL) or placebo four times daily (or twice daily) 1 day before and all days during CT. The patients were subsequently evaluated for OM incidence, severity, and duration using National Institute of Cancer Common Toxicity Criteria (NCI-CTC) criteria and an objective scoring system (1). After the start of the trials, negative results from new preclinical studies suggesting suboptimal formulation and/or dosing led to an interim analysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included in the interim analysis, with 116 patients on the TGF-beta3 four times daily and placebo arms. Most (72%) patients had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Although 98% (149 of 152) of patients experienced adverse events, only 14% (22 of 152) experienced events that were judged as possibly or probably related to the study drug (primarily gastrointestinal symptoms). No clinically relevant differences were seen between the treatment and placebo arms regarding safety, nor was there evidence for systemic absorption of TGF-beta3. Finally, there was no advantage of TGF-beta3 treatment regarding the incidence (TGF-beta3 four times daily versus placebo [46% versus 47%]), onset, or duration of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen. and patient population, TGF-beta3 was not effective in the prevention or alleviation of CT-induced OM.

Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation.

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients' peak OMAS scores and days with fever (body temperature > 38.0 degrees C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients' peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P <.05) correlated with all of the outcomes of interest except days with fever (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P <.01), (2) a 2.1-fold increase in risk of significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4) 2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001), and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P =.06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Oral administration of interferon-alpha induces a transient decline in oral mucosal immunoglobulins and an increase in interleukin-5.

Although administration of interferon-alpha (IFN-alpha) via the oral-mucosal route has shown efficacy in a variety of human and animal diseases, the mechanism of action of orally administered IFN is not clearly understood. To assess the possibility that IFN-alpha given via a lozenge alters the local mucosal immune system, immunoglobulins (Ig) and cytokines were measured in salivary secretions. Volunteers were given low doses of IFN-alpha and saliva was collected over a 24-h period. IgA and precursor IgM were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Salivary concentrations of interleukin-5 (IL-5), the T helper cytokine primarily responsible for the switch from IgM to IgA, were also determined. After oral administration of IFN-alpha, there was an initial decline in IgM and IgA followed by a return to baseline levels by 8-24 h. This change in Ig concentration was associated with a gradual increase in IL-5, consistent with the return of Ig to baseline as a result of modulation by Ig-mediating cytokines.

Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group.

BACKGROUND: An impediment to mucositis research has been the lack of an accepted, validated scoring system. The objective of this study was to design, test, and validate a new scoring system for mucositis that can be used easily, is reproducible, and provides an accurate system for research applications. METHODS: A panel of experts, convened to design an objective, simple, and reproducible assessment tool to evaluate mucositis with specific application to multicenter clinical trials, developed a scale that measured objective and subjective indicators of mucositis. Nine centers participated in the study's validation. Paired investigators at each center evaluated patients receiving chemotherapy or head and neck radiation. Objective measures of mucositis evaluated ulceration/pseudomembrane formation and erythema. Subjective outcomes of mouth pain, ability to swallow, and function were measured. Analgesia use for mouth sensitivity was recorded. RESULTS: One hundred eight chemotherapy and 56 radiation therapy patients were evaluated. Seventy-eight percent of chemotherapy patients and 64% of radiation therapy patients had clinically significant mucositis. Cumulative daily mucositis scores demonstrated a high correlation among observers. Using area under the curve analysis, it was found that for chemotherapy patients, the highest correlations (correlation coefficient > 0.92) occurred for the scores that selected the three highest daily values over the course of mucositis assessment. High interobserver correlations were noted for patients receiving radiation therapy. Objective mucositis scores demonstrated strong correlation with symptoms. CONCLUSIONS: The scoring system evaluated was easily used, showed high interobserver reproducibility, was responsive over time, and measured those elements deemed to be associated with mucositis. The use of concomitant symptomatic measurements appeared to be unnecessary.

Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.

BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.

Inhibition of the expression of hepatitis A and B viruses (HAV and HBV) proteins by interferon in a human hepatocarcinoma cell line (PLC/PRF/5).

AIMS/METHODS: PLC/PRF/5 is a continuous human hepatocarcinoma cell line whose genome contains integrated HBV DNA and which secretes two of the hepatitis B virus envelope proteins (HBs and PreS2). This line is also susceptible to infection by hepatitis A virus and was therefore used to compare the effects of interferon on protein synthesis of these two viruses and to assess the interactions which occur between them during infection. RESULTS: Results showed that recombinant interferon alpha 2-a inhibited the expression of the two hepatitis B virus envelope antigens (HBs and PreS2) and of the only hepatitis A virus antigen in a dose-dependent fashion. Comparison of the effect of interferon on antigenic protein production of these two viruses, showed stronger inhibition of hepatitis A virus capsid antigen than of hepatitis B virus envelope antigens. Infection with hepatitis A virus also downregulates the expression of the two hepatitis B virus proteins. CONCLUSIONS: Considering the absence of cytotoxic effects from the doses used, this study confirms the relevance of this cellular model for the study of antiviral cytokines in vitro. It also provides a further rationale for the clinical evaluation of the therapeutic potential of interferons in severe hepatitis cases due either to hepatitis A virus alone or to superinfection of hepatitis B virus carriers by hepatitis A virus.

Direct sequencing of hepatitis A virus strains isolated during an epidemic in France.

Direct sequencing of PCR products was used to study the VP1 region of the hepatitis A virus (HAV) genome (position 2199 to 2356) of nine strains isolated from human stools collected during a hepatitis A epidemic (western France, 1992), three strains from environmental samples (1990, 1991, and 1992), and two HAV cell culture isolates (the French strain CF53/Lyon and strain CLF). These viruses differed from CF53/Lyon (genotype I) by between 1 and 10.3%, and results indicated the existence of two groups of strains belonging to two different subgenotypes (IA and IB). With this sequencing technique it was possible to monitor the epidemiology of HAV and study its relations.

Antiviral activity of recombinant interferon-alpha on hepatitis A virus replication in human liver cells.

Human recombinant interferon-alpha (IFN-alpha) was assayed for its antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN-alpha resulted in concentration-dependent reduction of HAV antigen expression and HAV replication. IFN-alpha had a prophylactic effect, but was still effective when it was added after the infection, even at the end of the first replication cycle. An important increase in 2',5'-oligoadenylate synthetase activity in the IFN-treated human liver cells was observed. The antiviral effect of IFN-alpha could be attributed to the induction of this enzyme. Moreover we have shown that IFN-alpha and glycyrrhizin were synergistic in their antiviral actions against HAV. IFN-alpha emerged, from the present study, as a promising candidate for chemotherapy of severe forms of hepatitis A.

Comparison of the enzymatic properties of the two Escherichia coli lysyl-tRNA synthetase species.

In Escherichia coli, lysyl-tRNA synthetase activity is encoded by either a constitutive lysS gene or an inducible one, lysU. The two corresponding enzymes could be purified at homogeneity from a delta lysU and a delta lysS strain, respectively. Comparison of the pure enzymes, LysS and LysU, indicates that, in the presence of saturating substrates, LysS is about twice more active than LysU in the ATP-PPi exchange as well as in the tRNALys aminoacylation reaction. Moreover, the dissociation constant of the LysU-lysine complex is 8-fold smaller than that of the LysS-lysine complex. In agreement with this difference, the activity of LysU is less sensitive than that of LysS to the addition of cadaverine, a decarboxylation product of lysine and a competitive inhibitor of lysine binding to its synthetase. This observation points to a possible useful role of LysU, under physiological conditions causing cadaverine accumulation in the bacterium. Remarkably, these conditions also induce lysU expression. Homogeneous LysU and LysS were also compared in Ap4A synthesis. LysU is only 2-fold more active than LysS in the production of this dinucleotide. This makes unlikely that the heat-inducible LysU species could be preferentially involved in the accumulation of Ap4A inside stressed Escherichia coli cells. This conclusion could be strengthened by determining the concentrations of Ap4N (N = A, C, G, or U) in a delta lysU as well as in a lysU+ strain, before and after a 1-h temperature shift at 48 degrees C. The measured concentration values were the same in both strains.

Oral pilocarpine for radiation-induced xerostomia: integrated efficacy and safety results from two prospective randomized clinical trials.

PURPOSE: Pilocarpine hydrochloride administered in either a fixed-dose or in a dose-titration protocol three times a day for 12 weeks was evaluated for its ability to relieve symptoms of postradiation xerostomia and to improve saliva production. The studies were randomized, double-blind, placebo-controlled, multicenter clinical trials. A total of 369 patients who had received at least 40 Gy of radiation to the head and neck with clinically significant xerostomia were enrolled in the two studies. In the dose-titration study, 162 patients were enrolled and they received a thrice daily regimen of 2.5 mg tablets for first 4 weeks, 5.0 mg tablets for the second 4 weeks, and 10.0 mg tablets for last 4 weeks of a 12-week study. Patients in the titration study were allowed to down titrate following at least one dose escalation to alleviate bothersome side effects, if any. In the fixed dose study, 207 patients received either placebo, 5.0 mg, or 10.0 mg tablets t.i.d. for 12 weeks. METHODS AND MATERIALS: Patients were evaluated for symptomatic relief by responding to questionnaires using visual analog scales and categorical questions; and, for saliva production by sialometry. Questionnaires measured relief of intraoral dryness, improvement in overall condition (global response), oral discomfort, difficulty in speaking, chewing and swallowing, denture wearing, and usage of artificial saliva. Evaluations were conducted at baseline, and weeks 4, 8, and 12. RESULTS: There were statistically significant improvements in salivary flow in pilocarpine treatment groups vs. placebo. There was a significant improvement in the overall "global" condition of xerostomia associated with the use of pilocarpine in both studies. In the fixed-dose study, there were significant improvements in oral dryness, mouth comfort, ability to speak, and reduction in the use of oral comfort agents. The dose-titration study showed improvements in dryness that approached significance (p = 0.057) and a decreased use of oral comfort agents (p = 0.045). All pilocarpine dosages (2.5, 5.0, and 10.0 mg three times a day) were judged to be safe. Adverse experiences were those expected for a cholinergic agonist, with the most common being mild to moderate sweating. The incidence of these events increased by dose. CONCLUSION: It is concluded that in these studies pilocarpine produced clinically significant benefits with acceptable side effects and risks for the treatment of symptomatic postradiation xerostomia. The incidence of most adverse events increased with dose. Best results may require continuous treatment for more than 8 weeks with doses greater than 2.5 mg three times a day. A 5.0 mg thrice daily regimen produced the best clinical results when both efficacy and side effects were taken into consideration. There may be some patients who would experience some additional benefit by increasing the dose to 10 mg thrice daily.

Separate detection of the two complementary RNA strands of hepatitis A virus.

The minus strand of hepatitis A virus can be detected specifically by reverse transcription and polymerase chain reaction amplification in infected cell culture extracts. Several controls gave evidence that the amplified fragment actually used the minus strand as initial template. Non-thermostable reverse transcriptase was not efficient for this purpose because of self-priming of the positive-stranded viral RNA during the reverse transcription step. This problem was overcome by the use of the thermostable rTth DNA polymerase that also has reverse transcriptase activity in the presence of Mn2+.

Oral cytomegalovirus infection in an unrelated bone marrow transplantation with possible mediation by graft-versus-host disease and the use of cyclosporin-A.

Graft-versus-host disease remains as a significant sequela in allogeneic bone marrow transplantation patients. Reports of oral presentations of cytomegalovirus infection in this patient population are rare. Although the usual manifestation of oral cytomegalovirus is mucosal ulceration, we report a case that we believe reflects a dynamic among graft-versus-host disease, cytomegalovirus, and the use of cyclosporin A, commonly used as an immunosuppressive agent in bone marrow transplantation.

[Antiviral effect of recombinant interferon-alpha on hepatitis A virus replication in human liver cells]. / Effet antiviral de l'interféron-alpha recombinant sur la multiplication du virus de l'hépatite A dans des cellules hépatiques humaines.

Two recombinant interferons-alpha (IFNs-alpha) were assayed for their antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN alpha-2a and IFN alpha-2b resulted in concentration-dependent inhibition of HAV antigen expression and HAV infectivity at non toxic concentrations. Their selectivity indices, calculated as the ratio of the dose that reduced the number of viable cells to 50% (CD50) to the effective dose that inhibited 50% of viral antigen expression (ED50) were > 1000. Recombinant IFN-alpha emerged, from the present study, as a promising candidate for chemotherapy of hepatitis A.