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Biomedical subjects

M Schroeder

Publications and source records attributed to M Schroeder.

At least 109 records · Page 6Linked to original sources
PubMed1993

Actions of vesamicol on an alpha-bungarotoxin-sensitive neuronal nicotinic acetylcholine receptor.

Electrophysiology and binding studies were used to determine the actions of vesamicol [2-(4-phenylpiperidino)cyclohexanol (AH5183)] on an alpha-bungarotoxin-sensitive, neuronal nicotinic acetylcholine receptor in the nervous system of the cockroach, Periplaneta americana. Electrophysiological studies on an identified motor neurone revealed a reversible blocking action of (+/-)-vesamicol on the response to ionophoretically applied acetylcholine with an IC50 value of 8.0 x 10(-6) mol1(-1). The block was weakly voltage-dependent over the membrane potential range of -50 mV to -90 mV, and appeared to be non-competitive. No difference in potency was observed between the resolved stereoisomers. (+/-)-Vesamicol was found to suppress specific binding of 125I-labelled alpha-bungarotoxin to cockroach nervous tissue with an IC50 value of 5.1 x 10(-3) mol1(-1) and an estimated Hill coefficient of 0.73. Differences in the Hill coefficients were found when the resolved stereoisomers were tested separately. These data provide the first demonstration of a blocking action by vesamicol of a neuronal nicotinic acetylcholine receptor.

Animals↗
PubMed1992

Painful stimulation minimally increases the thermoregulatory threshold for vasoconstriction during enflurane anesthesia in humans.

Generalized autonomic stimulation enhances hemodynamic responses and may, in a similar fashion, facilitate thermoregulatory responses. We thus tested the hypothesis that painful stimulation increases the central temperature threshold for vasoconstriction during general anesthesia. Healthy volunteers were anesthetized with 1.3% end-tidal enflurane on 2 separate days. On 1 day (randomly assigned), painful stimulation was produced by tetanic electrical stimulation. On the other day, electrical stimulation was not given. Significant thermoregulatory vasoconstriction was defined as a forearm-fingertip skin-surface temperature gradient exceeding 4 degrees C. The distal esophageal temperature triggering significant vasoconstriction was considered the thermoregulatory threshold. The threshold was 35.5 +/- 0.8 degrees C during electrical stimulation and 35.1 +/- 0.6 degrees C without stimulation (P = 0.050, 95% confidence interval for the difference = 0-0.7 degree C). These data suggest that thresholds determined in nonsurgical volunteers will be slightly (but not clinically significantly) less than those in operative patients. Similarly, intraoperative vasoconstriction thresholds likely will be slightly less when surgical pain is prevented by simultaneous regional or local analgesia.

Adult↗
PubMed1992

Repeat plateletpheresis: the effects on the donor and the yield.

Requirements for HLA ot otherwise matched single-donor platelets may sometimes require repeat plateletpheresis of an individual donor. AABB standards permit the repeat collection of platelets by plateletpheresis of a single donor at 48-hour intervals, whereas recent recommendations from England state that a donor should not donate platelets more often than 12 times a year. To assess the effects of repeat plateletpheresis on the donor, we have studied the hematological indices and the product yields following every other day plateletpheresis of 13 normal donors who gave a total of 10 times during 22 days. The platelet count decreased in every case, with the lowest values reached at the third donation (day 5). The pre-donation count averaged 225 +/- 53 x 10(9)/l decreasing to 174 +/- 27 x 10(9)/l at the time of the 3rd donation then increasing by the 6th donation to 198 +/- 46 x 10(9)/l. The yield in the product decreased from 3.2 +/- 1.3 x 10(11) on day 1 to 2.6 +/- 0.8 x 10(11) for the third donation, returning thereafter to higher values. In spite of the expected and apparent stimulation of platelet production through feedback, the counts did not rebound above starting levels indicating a basic homeostatic mechanism. The donor WBC showed minimal changes during the study period, however there was a significant increase in the total number of lymphocytes by the 3rd procedure; this was corrected by the fifth procedure. The absolute number and ratio of T4 (helper) and T8 (suppressor) lymphocytes did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors↗
PubMed1992

Auditory event-related potentials in HIV-1 infection: a study in the drug-user risk group.

Features of event-related potentials (ERPs) may be sensitive and clinically useful markers of central nervous system infection by the human immunodeficiency virus (HIV-1); however, this application has not been studied in the risk group of intravenous drug users. Auditory ERPs generated by an "oddball" paradigm were analyzed for 39 male drug abusers as part of a multimodal assessment. Stage of HIV-1 infection was associated with prolongations of P1, N1, and P3 components of the ERP waveform. Only patients with full acquired immunodeficiency syndrome showed statistically significant increases in waveform prolongations. Specific neuropsychological deficits were not related to waveform latency prolongations.

AIDS Dementia Complex↗
PubMed1992

Thermoregulatory vasoconstriction during propofol/nitrous oxide anesthesia in humans: threshold and oxyhemoglobin saturation.

To determine the thermoregulatory effects of propofol and nitrous oxide, we measured the threshold for peripheral vasoconstriction in seven volunteers over a total of 13 study days. We also evaluated the effect of vasoconstriction on oxyhemoglobin saturation (SpO2). Anesthesia was induced with an intravenous bolus dose of propofol (2 mg/kg), followed by an infusion of 180 micrograms.kg-1 x min-1 for 15 min, and maintained with 60% nitrous oxide and propofol (80-160 micrograms.kg-1 x min-1). Central and skin surface temperatures and SpO2 (using two different pulse oximeters) were measured continuously; plasma propofol concentrations and arterial PO2 were measured at 15-min intervals. Volunteers were cooled with a circulating water blanket until definitive peripheral vasoconstriction was detected. The tympanic membrane temperature triggering vasoconstriction was considered the thermoregulatory threshold. Vasoconstriction developed on seven study days during propofol/nitrous oxide anesthesia at a central temperature of 33.3 +/- 1.0 degrees C (mean +/- SD) and plasma propofol concentration of 3.9 +/- 1.1 micrograms/mL. The thresholds during anesthesia were significantly lower than those during the control period (36.7 +/- 0.3 degrees C), but the correlation between plasma propofol concentrations and vasoconstriction thresholds was poor. On the remaining six study days, vasoconstriction did not develop despite central temperatures ranging from 32.1 to 32.7 degrees C. Corresponding propofol concentrations were 4.1-10.9 micrograms/mL. These data suggest that anesthesia with propofol, in typical clinical concentrations, and 60% nitrous oxide substantially inhibits thermoregulatory vasoconstriction. Vasoconstriction increased SpO2 by approximately 2% without a significant concomitant change in PO2. The observed increase in SpO2 probably reflects decreased transmission of arterial pulsations to venous blood in the finger.

Adult↗
PubMed1991

Cyclic-alternating versus response-oriented chemotherapy in small-cell lung cancer: a German multicenter randomized trial of 321 patients.

To test whether alternating chemotherapy is a favorable treatment modality in small-cell lung cancer (SCLC), 334 patients were randomized to receive either fixed cyclic-alternating treatment with ifosfamide/etoposide (IE), cyclophosphamide, doxorubicin, and vincristine (CAV), or response-oriented treatment with IE therapy up to maximal response and subsequently an immediate switch to CAV. In both arms, six cycles were given in 3-week intervals. After chemotherapy, patients with limited-stage disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation with 30 Gy was applied to all complete responders. No maintenance therapy was given to patients with complete response. Minimum follow-up was 2 years. Of 321 assessable patients, the overall response rate was 70% for cyclic alternating and 77% for response-oriented treatment. Complete remission (CR) rates were 26% versus 26%. The median survival times were 9.7 months for cyclic-alternating versus 10.7 months for response-oriented treatment; the 2-year survival rates were 11% versus 9%. In limited-stage disease (LD) patients, there was a median survival of 12.5 months versus 12.3 months and a 2-year survival rate of 21% versus 18%. In extensive-stage disease (ED) patients, median survival was 8.5 versus 9.1 months, and the 2-year survival rate 3% versus 4%. From these results, we conclude that the cyclic-alternating treatment according to the hypothesis of Goldie et al has no advantage in comparison to a sequential treatment strategy with an immediate switch to a second-line protocol at the time no further response to first-line therapy is seen. Our major aim in the treatment of SCLC is to administer an active regimen at any time during the course of treatment regardless of whether sequential or alternating therapy is used.

Adult↗
PubMed1989

Two daily doses of sucralfate or cimetidine in the healing of gastric ulcer. A comparative randomized study.

A double-blind, randomized study compared the healing of gastric ulcer during a twice-daily regimen of 2 g sucralfate or 400 mg cimetidine. The patients received the tablets one-half hour before breakfast and one-half hour before bedtime. The study included 76 patients with endoscopically proven gastric ulcer. Patients with ulcers less than 3 cm from the pyloric ring and patients with ulcers less than 3 mm in diameter were excluded from the study. Sixty-four patients completed the study. Healing was endoscopically assessed at four-week intervals for 12 weeks. After four, eight, and 12 weeks, the healing rates for cimetidine were 55, 81, and 94 percent, respectively; the healing rates for sucralfate were 52, 79, and 91 percent, respectively. No statistically significant difference was found between the two regimens. At 12 weeks, the risk of overlooking a difference in favor of one of the two dosage regimens was less than 20 percent. The results suggest that 2 g sucralfate twice daily is as effective in the healing of gastric ulcer as 400 mg cimetidine twice daily.

Adult↗
PubMed1989

Intralesional application of recombinant human tumor necrosis factor alpha induces local tumor regression in patients with advanced malignancies.

Fourteen patients with different advanced solid tumors were treated by intratumoral application of recombinant human tumor necrosis factor alpha. In five patients, local tumor regression occurred. However, the duration of response was short, implying a rapid development of resistance to rTNF-alpha application. The main clinical side-effects, including chills, fever, anorexia and fatigue, were similar to systemic rTNF-alpha treatment. Cardiovascular, pulmonary or metabolic toxicities were not observed. This study demonstrates that a high concentration of rTNF-alpha at the tumor site has the potential to induce local tumor regressions and, therefore, seems more reasonable for further clinical investigations, especially in combination with other cytokines.

Adolescent↗
PubMed1989

Experience of a German multicenter study group with ifosfamide in small cell lung cancer.

In three German multicenter randomized trials, which included 718 patients, the activity of ifosfamide in small cell lung cancer (SCLC) was tested. In study 1, IE (ifosfamide, 1.5 g/m2, days 1 through 5; etoposide, 120 mg/m2, days 3 through 5) alternating with CAV (cyclophosphamide, 600 mg/m2, days 1 and 2; doxorubicin, 50 mg/m2, day 1; vincristine, 2 mg, day 1) was compared with a response-oriented treatment with IE therapy up to maximum response and subsequently an immediate switch to CAV. After chemotherapy, patients with limited disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation (30 Gy) was given to all patients who achieved complete response (CR). A total of 324 patients were evaluable. Total response rate (CR + partial response [PR]) was 75% v 78% for the two treatment groups; the CR rate was 29% for both groups. Survival was nearly identical in both arms, with a median survival of 10.0 months for all patients, 12.0 months for those with limited disease (LD), and 7.5 months for those with extensive disease (ED). The 2-year survival rate was 11%. In study 2, IE was compared with PE (cisplatin, 90 mg/m2, day 1; etoposide, 150 mg/m2, days 3 through 5). A total of 141 patients were evaluable. Total response (CR + PR) rate was 65% for PE and 68% for IE; the CR rate for PE was 32% v 20% for IE. Survival favored PE with a median survival of 11.6 months v 9.4 months for all patients, 14.8 months v 11.0 months for LD, and 8.9 months v 7.5 months for ED. Two-year survival rates were 12% v 9% for all patients, 23% v 10% for those with LD, and 5% v 9% for those with ED. From these trials, we conclude that IE is an active and well-tolerated regimen for SCLC, and that PE may be superior to IE in limited-stage disease. Taking these results into account, we modified our chemotherapy protocols in study 3 and compared IAV (ifosfamide, 2 g/m2, days 1 to 5; doxorubicin, 25 mg/m2, days 1 and 2; vincristine, 2 mg, day 1) alternating with either PE or JE (carboplatin, 300 mg/m2, day 1; etoposide, 120 mg/m2, days 1 to 3). Interim results of 253 evaluable patients are as follows: CR + PR rate after 4 cycles was 68%; the CR rate was 28%; median survival was 11.6 months for all patients, 14.8 months for LD, and 10.2 months for ED.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1988

[Results of 2 multicenter therapy studies in inoperable non-small cell bronchial cancer].

A total of 166 patients with non-small cell lung cancer (NSCLC) were included in two multicenter trials testing different treatment regimens. In study I, 116 patients received 4 cycles of aggressive polychemotherapy consisting of cis-platinum 100 mg/m2 (day 1), etoposide 100 mg/m2 (days 4-6), and vindesine 3 mg/m2 (day 1) (CEV); patients without distant metastases subsequently received chest irradiation with 50 Gy. In study II, 50 patients were treated with monochemotherapy consisting of etoposide 250 mg/m2 (days 1-3), and ifosfamide 5 g/m2 as 24-h infusion (day 29). While this program was repeated in responders with extensive disease (ED), patients with limited disease (LD) subsequently received chest irradiation with 50 Gy using 20 mg/m2 cis-platinum weekly as a radiosensitizer. Response rates (CR + PR) to chemotherapy were higher in study I than in study II, and were 26% (CR 3%) vs. 8% (CR 0%) for all patients, 18% (CR 0%) vs. 4% (CR 0%) for ED, and 45% (CR 11%) vs. 13% (CR 0%) for LD. The increase in response rates by radiotherapy was marginal in study I (CR + PR 47%, CR 18%), but remarkable in study II (CR + PR 42%, CR 29%). While median survival was slightly longer in study I than in study II for ED (7.7 vs. 6.6 months) and LD (14.4 vs. 12.0 months), the 2-year survival rate was in favor of study II (10% vs. 25%). Toxicity was clearly more pronounced in study I, including 3 lethal complications and 16 discontinuations of therapy due to side effects or refusal. Thus, while in ED the efficacy of both treatment regimens was very restricted, in LD radiotherapy with cis-platinum as a radiosensitizer achieved a relatively high 2-year survival rate which justifies further testing of this treatment strategy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.

A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Incidence of recurrence and long-term survival in small cell bronchial carcinoma].

Analyses of relapse in small cell lung cancer (SCLC) were performed in 443 evaluable patients included in two multicenter trials. The time to first progression mainly depended on best response to therapy. Nearly all patients with no change (NC) suffered from progression within 6 months. In patients with partial remission (PR), progression occurred within 12 months in nearly all cases. If complete remission (CR) was achieved, no relapse was seen within the first 6 months after the onset of treatment. Between the 6th and 8th month a slowly increase and after the 8th month a rapid increase of relapse was noticed. In the majority of patients with limited disease relapse was localized in the area of the primary tumor, whereas in patients with extensive disease relapse mostly was due to the development of distant metastases. Of the 443 patients, 35 achieved 2-year survival (8%). Main prognostic factors for the achievement of 2-year survival were extent of disease and sex. Patients with distant metastases and CR had a poor chance of achieving a 2-year survival, while patients without distant metastases and CR had a 30% chance. Females with limited disease and a Karnofsky score of 70% or more had a 40% chance of achieving 2-year survival, the corresponding probability for males was less than 10%. Because of the high frequency of relapse in SCLC, the stabilization of best response has to be considered as a main objective in therapy. In our opinion, two different strategies may be useful in order to achieve higher 2-year survival rates: a) periodic controls and renewal of therapy as soon as possible after relapse has occurred or b) reinduction therapy in intervals of about 8 weeks or more in order to delay or prevent the development of relapse. To find out if one of these strategies is superior to the other, is one of the objectives of our new randomized trial in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial.

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

Adult↗
PubMed1986

Two randomized trials for alternating polychemotherapy of small cell lung cancer.

Patients with small cell carcinoma of the lung (SCCL) were treated in two multicenter trials with different cytostatic drug regimens including ifosfamide. In the first randomized study, including 306 patients, alternating chemotherapy with VP 16, ifosfamide, vindesine (VPIV), adriamycin, cisplatinum, vincristine (APO), and cyclophosphamide, methotrexate, CCNU (CMCC) was compared against standard treatment with ACO (adriamycin, cyclophosphamide, vincristine). It was shown that the alternating therapy resulted in a higher response rate (88% vs 78%) and a longer median survival time (11 months vs 10 months). Regarding toxicity, VPIV was similar to ACO, whereas APO and CMCC had more side-effects, leading to an increase in the number of drop-outs. In the second randomized study 144 patients were treated either with ifosfamide/VP 16 (IVP) or with cisplatinum/VP 16 (PVP). In the case of no further response, no change, or progression the induction therapy was changed to ACO. Interim analyses show that both regimens have similar therapeutic effects; but higher toxicity was observed in patients treated with cis-platinum/VP 16 than in patients treated with ifosfamide/VP 16. According to the response rate in patients treated with ACO after first-line therapy there was less cross-resistance of IVP than of PVP to ACO.

Age Factors↗
PubMed1984

Organization of microtubules in stabilized meristematic plant cells revealed by a rat monoclonal antibody reacting only with the tyrosinated form of alpha-tubulin.

A rat monoclonal antibody against yeast tubulin (clone YL 1/2; Kilmartin et al., 1982) that reacts specifically with mammalian alpha-tubulin carrying a carboxyterminal tyrosine residue (Wehland et al., 1983) was used to localize microtubules in plant cells derived from onion root apices (Allium cepa L.). YL 1/2 reacted with all types of microtubular arrays known to occur in higher plant meristematic cells such as interphase cortical microtubules, pre-prophase bands, the mitotic spindle and phragmoplast microtubules. The specific labeling of microtubules in isolated cells from onion root tips by YL 1/2 indicates that plant cells like animal cells contain tubulin tyrosine ligase, the enzyme which posttranslationally modifies alpha-tubulin. This enzyme could be involved in the dynamic regulation of microtubular arrays in all eukaryotic cells.

Antibodies, Monoclonal↗