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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 235 records · Page 13Linked to original sources
PubMed1996

Angiogenic growth factor mRNA responses in muscle to a single bout of exercise.

A major adaptation to exercise is new capillary formation in skeletal muscle. On the basis of angiogenesis in tumors and during development, several angiogenic growth factors may be involved, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1 (TGF-beta 1). In 9-wk-old female Wistar rats, mRNA expression for these three growth factors in gastrocnemius muscle was examined by quantitative Northern analysis after a single 1-h run at 15 or 20 m/min at 10 degrees incline in room air. A third group ran at 15 m/min in 12% O2, and resting control groups were included at inspired O2 fractions of 0.21 and 0.12. Exercise significantly increased mRNA levels two- to fourfold, which was evident over the first 4 h postexercise; by 8 and 24 h, mRNA levels returned to baseline. For all three factors, mRNA levels were significantly higher after exercise at 20 than at 15 m/min. Hypoxia at rest doubled VEGF and TGF-beta 1 message but had no effect on bFGF. Hypoxic exercise further raised VEGF mRNA levels but had no effect on the other factors. We suggest that VEGF, bFGF, and TGF-beta 1 may be involved in the angiogenic response to exercise and that reduced intracellular PO2 (as occurs during normoxic exercise) may be part of the stimulus to such growth factor production.

Animals↗
PubMed1996

Management of Toxicities of Combined Modality Therapy for Intrathoracic Malignancies.

BACKGROUND: Combined radiation and chemotherapy for intrathoracic tumors can produce appreciable morbidity. Apprehension about the severity of these toxicities may inhibit optimal patient care. METHODS: The literature on recognition, diagnosis, prophylaxis, and management of these toxicities is reviewed and combined with the experiences of the authors to produce management recommendations. RESULTS: Toxicities include acute and chronic esophagitis, early and late pneumonitis with fibrosis, myelosuppression, and neurologic deficits. Measures are available to minimize their severity and to reduce their impact on the patient. CONCLUSIONS: The morbidity of combined radiation and chemotherapy patients with intrathoracic tumors can be minimized by recognizing potential toxicities and by applying appropriate prophylactic and management measures.

Journal Article↗
PubMed1996

[Hip joint arthrodesis using the cobra plate. Indication, technique, outcome].

In the era of successful total hip replacement, hip arthrodesis has become an infrequent surgical procedure. Current indications are severe deterioration of the hip joint with a painful, reduced range of motion in young patients, such as disorders subsequent to sepsis of the hip joint, slipped capital epiphysis, Perthes' disease and trauma with contraindications for a total joint replacement. Another important indication is paralysis or musculature loss. From 1980 to 1990, 20 consecutive patients underwent a hip arthrodesis with a cobra plate and were evaluated. None of the patients was lost for follow-up; complications occurred in 5 out of 25 cases (20%). All patients had radiographic evidence of union, 2 patients required re-osteosynthesis and bone grafting. In two cases infection occurred. In one case the position of the fused join went into abduction. Thirteen patients were able to walk free of pain; however, 5 patients were disappointed with the arthrodesis result because of the handicap involved with a fused hip. Hip arthrodesis using the cobra plate is a technically demanding operation, but immediate mobilization and partial weight bearing are facilitated. There is little risk of non-union compared to other surgical procedures. If the technique is correct functional problems will be rare.

Adolescent↗
PubMed1996

Paclitaxel and cisplatin in patients with non-small cell lung cancer: results of a phase II trial.

We performed a clinical phase II trial of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small cell lung cancer (NSCLC), using a 3-hour infusion of paclitaxel followed by a 1-hour infusion of cisplatin. Treatment was repeated every 21 days, for a maximum of six cycles. The patients received paclitaxel 175 mg/m2 followed by cisplatin 75 mg/m2. At present, 52 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.7%) NSCLC have been entered into this ongoing trial. Ten (19%) of the patients are women and 42 (81%) are men. With 197 courses of chemotherapy given, all 52 patients are evaluable for toxicity. Hematologic toxicities were moderate: World Health Organization (WHO) grade 3 or 4 neutropenia occurred in 38.7% of the cycles (47.7% of patients), and WHO grade 3 or 4 thrombocytopenia was observed in 1.5% of cycles (3.8% of patients). Other toxicities consisted mainly of WHO grade 2 or 3 alopecia and nausea/vomiting. World Health Organization grade 1 or 2 polyneuropathy occurred in 30.4% and grade 3 or 4 only in 1% of all courses. Of 40 patients evaluable for response, a complete remission was noted in one patient, a partial remission occurred in 13 patients (32.5%), stable disease was seen in 14 patients (35%), and disease progressed in 12 patients (30%). These results suggest that the combination of paclitaxel and cisplatin is active and tolerable in the treatment of NSCLC. The efficacy of the combination seems high in this poor-prognosis population.

Adult↗
PubMed1996

Phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer.

Few cytotoxic agents tested in adequate phase II trials involving patients with non-small cell lung cancer have produced single-agent response rates greater than 15%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of them, with reported response rates ranging from 21% to 36%. Platinum-based regimens have been key to the development of the most effective combination therapies for NSCLC. We are currently investigating the efficacy and toxicity of combining paclitaxel (175 mg/m2) given by 3-hour infusion, followed by cisplatin (75 mg/m2) via 1-hour infusion, on a 21-day schedule for the treatment of 75 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.6%) non-small cell lung cancer. Patient characteristics include a median age of 58 years (age range, 28 to 75 years) and a median Eastern Cooperative Oncology Group performance status of 2; 19 patients (25.3%) are women and 56 (74.7%) are men. All patients received standard prophylactic premedication as well as adequate hydration. To date, 75 subjects and 328 courses are evaluable for toxicity. Hematologic toxicities have been moderate; grade 3 or 4 neutropenia occurred in 37% of cycles (50% of patients), and grade 3 or 4 thrombocytopenia was observed in only 2% of cycles (2% of patients). Other notable toxicities were World Health Organization grade 2 or 3 alopecia and nausea/vomiting. Grade 1 or 2 peripheral neuropathy occurred in 26% and grade 3 or 4 in only 1% of all courses. Of 67 patients evaluable for response, complete remission was noted in three (5%) patients, partial remission in 25 (37%) patients, stable disease in 22 (33%) patients, and progressive disease in 17 (25%) patients. These results suggest that combination paclitaxel/cisplatin is active and well tolerated in the treatment of non-small cell lung cancer.

Adenocarcinoma↗
PubMed1996

Single-agent paclitaxel as a 3-hour infusion.

This ongoing phase II trial of patients with inoperable stage IIIB-IV non-small cell lung cancer is seeking to determine the efficacy and toxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour infusion. The 58 patients now evaluable met standard eligibility requirements, including no prior chemotherapy. Paclitaxel 225 mg/m2 was delivered every 3 weeks for up to 10 courses, depending on patient response. All patients were evaluable for toxicity and 50 were evaluable for response. There were no complete responses, 12 patients had partial responses, 12 had progressive disease, and 26 had no change. The median time to response was 8.7 weeks; the median survival was 10 months. Leukopenia, when observed, was grade 1 or 2 in all but one case. Likewise, all nonhematologic effects were mild, with the exception of one case of grade 3 gastrointestinal toxicity. The 3-hour infusion schedule is more convenient, and the authors feel that the safety of the schedule is confirmed by these results. However, the efficacy of the shortened schedule, compared with a 24-hour infusion, remains to be proven.

Adult↗
PubMed1996

Experience with the modified Meek technique.

In 1958 Meek described the so called Meek-Wall dermatome to cut postage stamp skin grafts. This method was eclipsed by the introduction of mesh skin grafts. In 1993 Kreis and colleagues reintroduced a modified Meek technique using a dermatome running on compressed air. This technique has been used in our burn unit since August 1994. The aim of this paper is to compare the modified Meek technique with the mesh graft technique. Within a period of 20 months 41 patients were grafted using the modified Meek technique. The mean TBSAB was 54.4% with 50.0% full thickness burns. All patients were excised early. The expansion ratio was 1:4 and 1:6. In 20 patients the Meek technique was used exclusively for grafting of the trunk and the extremities with the exception of face, neck and hands. In 3 patients with a mean TBSAB of 68.3% a combination of postage stamp autologous skin grafts and cultured epithelial autografts (CEA) was applied. Compared with the mesh graft technique the Meek technique showed the following advantages: 1. The Meek method provides the true expansion ratio. 2. Small graft remnants can be utilized. 3. Grafting of full thickness burns up to 70 to 75% TBSAB becomes possible with one harvest of the donor sites. 4. The reliability of graft take is equal or better. 5. Epithelialization is achieved within 3 to 4 weeks depending on the expansion ratio. 6. The combination of widely expanded postage stamp split thickness grafts and CEA provides an excellent take rate and durable wound closure within a short time and avoids the problems associated with the engraftment of CEA on fascia. The method is simple but more demanding than the mesh technique. Compared with the mesh graft technique the preparation of Meek grafts is more time consuming and requires more staff than the Mesh technique. The cost of materials is higher. In our experience complete coverage of the Meek grafts with an overlay of meshed allografts after removal of the gauze as recommended by Kreis is not necessary using the 1:4 expansion ratio. Greater expansion ratios necessitate an overlay with meshed allografts. Regarding the scar formation no significant differences were observed compared with the mesh graft technique. In conclusion the modified Meek technique is reliable and simple to perform. This technique provides a sufficient expansion ratio enabling to graft patients with burns up to 75% TBSA with only one harvest of donor sides and without the necessity of CEA. In our opinion the Meek technique is reliable and simple to perform. This technique provides a sufficient expansion ratio enabling to graft patients with burns up to 75% TBSA with only one harvest of donor sides and without the necessity of CEA. In our opinion the Meek technique is advantageous in patients with burns greater than 45% TBSAB. In smaller burns mesh grafts should be used because of lower material cost and staff requirements. Especially in extensively burned patients the Meek technique may be cost effective avoiding the need of CEA.

Adolescent↗
PubMed1995

Induction of responsiveness in superantigen-induced anergic T cells. Role of ligand density and costimulatory signals.

The bacterial superantigen staphylococcal enterotoxin B (SEB) induces in vivo a state of anergy defined by the inability of V beta 8+ CD4+ T cells to produce IL-2 upon restimulation in vitro. However, restimulation in vivo triggers a burst of acutely released lymphokines including IL-2 and TNF, paralleled by up-regulation of lymphokine-specific mRNA. Since anergy as defined in vitro appears not to operate in vivo, we analyzed parameters able to induce responsiveness in anergic T cells. We show here that in vitro stimulation of anergic T cells with competent Ag-presenting cells induces responsiveness, provided the APC (activated B cells or dendritic cells) present high concentrations of SEB. Crosslinking of CD28 molecules on anergic T cells could substitute the requirement for competent APC. Quantitation of TCR threshold by determining the SEB concentrations able to trigger half-maximal T cell responses revealed that anergic and normal T cells exhibited the same TCR threshold for the expression of functional IL-2 receptors (IL-2R), yet the TCR threshold for induction of IL-2 production was 10- to 100-fold elevated in anergic T cells. TCR threshold for normal and anergic T cells was further dependent on the type of APC, i.e., costimulus-competent APC required 100-fold less SEB. The results indicate that extrinsic factors such as ligand concentration and costimulus competence of APC can overcome the heightened TCR threshold of anergic T cells, thus reverting anergy into responsiveness.

Animals↗
PubMed1995

Negative-acting factor and superantigen are separable activities of the mouse mammary tumor virus long terminal repeat.

The open reading frame contained within the long terminal repeat (LTR) of mouse mammary tumor virus encodes Naf, a negative regulator of transcription, as well as a superantigen activity, Sag, which causes the deletion of specific classes of T cells. In the present study, the effect of Naf expression on different promoters and the coding requirements for Naf and Sag have been investigated. Sag activity was found to require only sequences in the LTR, whereas sequences located within the gag gene were additionally required for functional Naf activity. Surprisingly, both the classic promoter and a recently described promoter located in the LTR can give rise to both functional Naf and Sag. Further analysis of Naf revealed that the downregulatory effect was mediated by sequences located in the LTR and that heterologous promoters were also affected by Naf.

Animals↗
PubMed1995

Differential effects of the immunosuppressive agents cyclosporine and leflunomide in vivo. Leflunomide blocks clonal T cell expansion yet allows production of lymphokines and manifestation of T cell-mediated shock.

The effects of leflunomide and CsA on immune responses in vitro and in vivo were investigated. Like CsA, leflunomide inhibited mitogen- or antigen-driven T cell proliferation in vitro. However, leflunomide impaired neither the capability of T cells to produce IL-2 and IL-4, nor the expression of IL-2R, that is, the acquisition of competence. In contrast to CsA, the IL-2-driven growth of secondary T cells was blocked by leflunomide. Cell cycle analyses revealed that activated T cells did not enter S phase of the cell cycle in the presence of leflunomide. Next, the effects of leflunomide and CsA on the T cell response toward the bacterial superantigen (SAg) staphylococcal enterotoxin B (SEB) were analyzed in vivo. SEB-induced early deletion (apoptosis) of a fraction of SEB-reactive V beta 8+ T cells and IL-2R expression were not impaired by either CsA nor leflunomide. On the other hand, both CsA and leflunomide prevented V beta 8-selective clonal T cell expansion and generation of SEB-specific cytolytic activity. In contrast to CsA, leflunomide treatment permitted in vivo SEB-induced production of T cell-derived lymphokines (IL-2 and TNF). Further, leflunomide failed to protect D-galactosamine-sensitized mice from SEB-induced, T cell-mediated lethal shock, whereas CsA was fully protective. Manifestation of SEB-induced T cell anergy was not impaired by leflunomide. Our results provide evidence that CsA and leflunomide differ significantly in their functional properties to suppress immune responses in that both agents inhibit T cell functions linked to clonal expansion, while leflunomide does not inhibit lymphokine secretion and thus permits lymphokine-mediated immune functions.

Animals↗
PubMed1995

Bacterial superantigens induce T cell unresponsiveness in B cell-deficient mice.

Bacterial superantigens such as staphylococcal enterotoxin B (SEB) cause in vivo a profoud and long-lasting state of unresponsiveness in ligand-reactive T cells. To test whether presentation of SEB by small resting B cells to ligand-reactive T cells is essential for the induction of T cell unresponsiveness, we analyzed the effect of SEB in B cell-deficient mice. We observed T cell deletion and T cell unresponsiveness in both B cell-deficient mice and control mice. We conclude that presentation of SEB by resting B cells is not a prerequisite for the induction of T cell unresponsiveness in vivo.

Animals↗
PubMed1995

Heart rate fluctuations of lower frequencies than the respiratoryrhythm but caused by it.

In conscious adult rabbits, "classical" respiratory sinus arrhythmia does not occur because the respiratory frequency (RF) always exceeds half the heart rate (HR). However, slow HR fluctuations, not synchronous with the respiratory rhythm but affected by it, occur systematically. We have shown that these can be calculated by using aliasing rules. During general anaesthesia, when the RF decreases so that respiratory frequency is less than half the heart rate, classical respiratory sinus arrhythmia occurs and can be greatly reduced by vagal blockade. The slow HR fluctuations which are not synchronous with the respiratory rhythms, but are affected by it are mainly vagally mediated, because vagal blockade virtually eliminates them.

Animals↗
PubMed1995

Frequency of toxic shock syndrome toxin- and enterotoxin-producing clinical isolates of Staphylococcus aureus.

In 183 clinical isolates of Staphylococcus aureus, toxic shock syndrome toxin was detected in 13.7%, enterotoxin A in 20.2%, enterotoxin B in 7.7%, enterotoxin C in 5.5% and enterotoxin D in 3.3%. Seventy-three (39.9%) of the strains were found to produce one or more toxins. Multiple secretion of toxins was rare (< 1% of all strains) except for the combinations enterotoxin A with toxic shock syndrome toxin and enterotoxin A with enterotoxin D. These combinations were observed at significantly higher frequencies (4.9% and 2.2%, respectively) than would have been expected from values calculated from respective individual frequencies (0.88% and 0.06%) (p < 0.0001). In comparison with Staphylococcus aureus strains isolated from miscellaneous material, Staphylococcus aureus blood culture isolates produced enterotoxin D in significantly larger amounts and at higher frequencies (p = 0.01 in both cases). These toxins might play an important pathogenic role in Staphylococcus aureus infections.

Bacterial Toxins↗