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Biomedical subjects

C Frank

Publications and source records attributed to C Frank.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Cellular immune defect caused by postoperative irradiation in patients with squamous epithelial carcinomas of the upper aerodigestive tract].

The effect of locoregional postoperative radiation therapy on cellular immunity was investigated in 11 patients with head and neck cancer. During the course of the radiation therapy, total lymphocyte counts, CD8+ lymphocyte counts and especially CD4+ lymphocyte counts decreased significantly. The mean CD4+ lymphocyte counts dropped from 739/microliters to 183/microliters (p < 0.001) and the average CD4+/CD8+ ratio also decreased significantly. In addition all patients showed impaired in vitro lymphocyte stimulation responses to several mitogens, with reductions found to be 10% to 50% of normal responses. Within 3-4 weeks after radiation therapy there was a slight increase of CD4+ lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency to normalization. These results indicate that locoregional postoperative radiation therapy in patients with head and neck cancer can induce a severe impairment of cellular immunity.

CD4 Lymphocyte Count↗
PubMed1995

5-Fluorouracil prodrug: role of anabolic and catabolic pathway modulation in therapy of colorectal cancer.

Following p.o. administration to rats bearing advanced colorectal carcinoma, Ftorafur (FT) is converted to 5-fluorouracil (FUra) by microsomal P450 in the liver. To optimize the therapeutic selectivity of the FUra generated from FT, three approaches were utilized: (a) inhibition of FUra degradation to dihydrofluorouracil by uracil as an alternative substrate for uracil reductase in the molar ratio of 4 uracil:1 FT (UFT); (b) modulation of drug inhibition of thymidylate synthase by leucovorin (LV); and (c) by increasing the level of FUra incorporation into cellular RNA by N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartate transcarbomylase. The maximum tolerated dose (MTD) of FT and UFT, administered 3 times a day for 28 days, was 150 mg/kg/day and 60 mg/kg/day, respectively. The MTDs were not significantly modified by LV (150 or 600 mg/kg/day), administered by the p.o. route with the drugs, or by PALA (100 mg/kg) administered weekly by the i.v. route. The dose-limiting toxicity of FT alone and in combination with the modulators was stomatitis. The severe alopecia observed with FT alone was reduced significantly by uracil. At the MTD, the antitumor activity of UFT was superior to those of FT and FUra alone and in combination with LV and/or PALA. The 3-month sustained complete tumor regression for UFT, FT, and FUra was 38%, 0%, and 13% (for the weekly schedule), respectively. Although uracil, LV, and PALA individually increased the antitumor activity of FT at its MTD, the combination of the three modulators produced the highest therapeutic efficacy in rats bearing advanced colorectal carcinoma, in which 100% of the treated animals achieved complete and sustained tumor regression. The therapeutic efficacy observed with FT modulation could not be achieved with FUra administered by different schedules, each at its MTD alone or in combination with either LV or PALA. In brief, modulation of FT produced greater therapeutic efficacy and selectivity than FUra. Furthermore, the combined use of modulators capable of inhibiting the degradation pathway of FUra and potentiating the effects of the anabolic metabolites action appears to offer the greatest therapeutic potential.

Animals↗
PubMed1994

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.

Adult↗
PubMed1994

Conservative treatment of breast cancer: modified irradiation technique for women with large breasts.

Seven patients with large, pendulous breasts received external beam irradiation to the whole breast (50 Gy in 25 fractions plus boost) after lumpectomy. A special breast holding mask was shaped for each patient. Three-dimensional treatment plans and dose-volume histograms of the same patient with and without a mask were compared. Day-to-day variance was checked. This technique provides improvements in dose homogeneity, reproducibility, and sparing of normal tissues. Cosmetic outcome at present is good.

Breast↗
PubMed1994

Neural modulation of muscle contractile properties during fatigue: afferent feedback dependence.

H reflex amplitudes, an indirect measure of the excitability of the alpha motoneuron pool, were recorded from 10 males during fatigue induced by submaximal, isotonic, voluntary contractions of the soleus muscle. H reflex changes were correlated with electromyographic changes (mean power frequency (MPF); root mean square (rms EMG)), under ischemic and non-ischemic conditions. The purpose of the ischemia was to block transmission of Ia and possibly Ib afferents to assess whether changes in sensory feedback had any effect on alpha motoneuron and EMG activity during fatigue. Significant interactions were found between ischemic and non-ischemic conditions. After an initial decrease (1.21 +/- 0.56 mV to 0.54 +/- 0.39 mV), H reflex amplitudes increased during non-ischemic trials (0.54 +/- 0.39 mV to 1.13 +/- 0.84 mV). Under ischemic conditions H reflex amplitudes decreased (2.11 +/- 1.10 mV to 0.70 +/- 0.74 mV; P < 0.003). During non-ischemic conditions, MPF decreased across 5 consecutive trials (157.7 +/- 17.9 Hz to 124.7 +/- 17.2 Hz), as compared to an increase under ischemic conditions (132.8 +/- 21.2 Hz to 197.1 +/- 53.6 Hz; P < 0.001). Root mean square amplitude decreased during the non-ischemic trials (31.07 +/- 14.62 mV to 25.98 +/- 8.26 mV). A greater decrease was noted during the ischemic trials (34.00 +/- 23.61 mV to 4.95 +/- 3.77 mV; P < 0.001). Data suggest that the CNS modulates muscle contraction in order to preserve force output and neuromuscular transmission during fatigue. This modulation appears dependent on Ia and/or Ib afferent feedback.

Adult↗
PubMed1994

Pertussis toxin prevents neomycin-induced calcium-dependent electrophysiological effects in rat hippocampal slices.

1. The influence of pertussis toxin has been studied on the effects of neomycin on CA1 field potentials in rat hippocampal slices in order to determine a role played by G protein in the modulation of synaptic transmission by the drug. 2. Neomycin (500 microM), within 30 min significantly (P < 0.01) decreased the magnitude of the somatic CA1 excitatory postsynaptic potentials (EPSP) and population spike (PS) in control hippocampal slices. 3. Neomycin (500 microM), within 30 min failed to significantly affect the magnitude of the somatic CA1 EPSP and PS in slices obtained from animals treated intracerebroventricularly (ICV) with 1-2 micrograms of pertussis toxin 3 days before. 4. The results demonstrated that pertussis toxin prevents some electrophysiological effects of neomycin, suggesting a role of G protein in the modulation of the aminoglycoside antibiotic on central synaptic transmission.

Action Potentials↗
PubMed1994

Selective reduction of hippocampal dentate frequency potentiation in aged rats with impaired place learning.

Induction of posttetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from a) young 6-month-old Sprague-Dawley (SD) rats, all of them performing well in the Morris Maze, and b) aged SD 20-month-old and Fischer 344 24-month-old rats showing different degrees of ability in the same test. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum moleculare, a significant difference was found in the percent of dentate PTP induction in hippocampal slices obtained from rats of different ages. Specifically, dentate PTP induction was significantly (p < 0.01) higher in slices obtained from young SD rats, and from old SD rats with a better performance in the Morris maze, escape latency less than 10 s and 150 cm, than in slices obtained from old SD or Fischer 344 rats that had shown poor performance in the Morris Maze. On the contrary, no significant differences were found in the percent of dentate LTP in hippocampal slices obtained from rats of different strains and ages. The data demonstrate that the induction of hippocampal dentate high-frequency PTP is selectively reduced in old rats with impaired Morris Maze performance.

Aging↗
PubMed1994

Ligament tension affects nuclear shape in situ: an in vitro study.

This study was carried out to test the hypothesis that a relationship exists between ligament tension and ligament cell geometry. Rabbit knee joints were positioned at 70 degrees of joint flexion and the medial collateral ligament (MCL) was mechanically isolated and the femur-MCL-tibia complex was stretched or compressed by displacing the crosshead of a materials testing machine: -2.0 mm (relative compression), 0.0 mm (a reproducible no-load starting point), +/-0.7 mm or + 1.4 mm (relative tension). Each MCL complex was then fixed immediately in 10% neutral buffered formalin. Contralateral knees were dissected similarly with MCLs exposed and fixed in situ at 70 degrees of flexion. Subsequent to histological processing, measurements were made of the profiles of fibrocyte nuclei (since previous work has shown that nuclear shape closely approximates fibrocyte shape) that were located in the central portion of each MCL midsubstance using a video-based computerized morphometry system. Results showed that the dimensions of nuclei in the midsubstance of experimental MCLs were significantly longer and thinner at crosshead displacements that corresponded to increased ligament tension. At +1.4 mm of displacement fibrocyte nuclei were approximately 4 microm longer and 1 microm thinner than those fixed at 0.0 mm, an observation supported by a statistically significant increase in the mean maximum-to-minimum-diameter ratio and a significant decrease in mean cell roundness. These results strongly suggest that mechanical load can directly affect ligament fibrocyte geometry in situ. If a similar phenomenon also occurs in vivo, the metabolism of ligament fibrocytes may be influenced considerably by their loading history.

Animals↗
PubMed1994

Results of radiotherapy and combined modality treatment in early stage high grade non-Hodgkin's lymphoma.

PURPOSE: In combined modality treatment of early stage, high grade non-Hodgkin's lymphoma disease status after initial chemotherapy was analyzed to evaluate the impact of remission status on survival. Analysis of relapse patterns was performed to assess efficacy of radiation doses and volume. PATIENTS AND METHODS: Fifty-four patients with early stage high grade non-Hodgkin's lymphoma were treated with radiotherapy alone or with initial chemotherapy followed by involved field irradiation. Overall survival, relapse-free survival and relapse patterns were analyzed. RESULTS: In patients treated with radiotherapy alone (stage I n = 15, stage II n = 8) overall survival rate was 69%, relapse-free survival was 35% at 3 years. Patients achieving combined modality treatment (stage I n = 5, stage II n = 26) showed an actuarial 3 year overall survival of 78%, relapse-free survival was 62%. Complete remission status after chemotherapy was an important factor for durable disease control. Those patients, who achieved complete remission after chemotherapy showed an actuarial relapse-free survival of 75% at 3 years. Patients with partial remission or progressive disease after chemotherapy had a poor outcome (relapse-free survival 35%). Analysis of the first manifestation of lymphoma progression after radiotherapy in relation to the treatment portals demonstrated radiotherapy to be highly effective in achieving local control. Only 8% of recurrences occurred within the irradiated volume. 56% of failures were found in non-contiguous sites to the former radiation portals. CONCLUSION: This analysis suggests that effective chemotherapy in combination with involved field radiotherapy in CS I (with risk factors) and especially in CS II patients is necessary to control extension of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1993

Protective actions of 21-aminosteroids and MK-801 on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of the 21-aminosteroids, U-74500A and U-78517F (drugs endowed with lipid peroxidation inhibitor properties) were tested on hypoxia-induced functional failure in rat hippocampal slices. For comparison, the effects of the non-competitive N-methyl-D-aspartate antagonist, dizocilpine (MK-801) were studied. Perfusion of slices with 50 microM of MK-801 or with 50-100 microM of U-78517F, but not with 100-200 microM of U-74500A, significantly (P < 0.01) increased the incidence of reappearance of the CA1 population spikes after reoxygenation in rat hippocampal slices subjected to a 45-min hypoxic period followed by a 45-min reoxygenation period. Perfusion of slices with 12.5 microM of MK-801 plus 12.5 microM of U-78517F significantly (P < 0.05) increased the incidence of reappearance of the CA1 population spikes after reoxygenation with respect to perfusion of slices with 12.5 microM of U-78517F alone or with 12.5 microM of MK-801 alone. The results show that 21-aminosteroids have protective effects against hypoxia-induced functional failure in rat hippocampal slices. In addition, the data show that, under the same experimental conditions, the NMDA receptor antagonist, MK-801, was also able to improve hypoxia-induced functional failure. On the whole, the results suggest that the hypoxia-induced functional electrical failure might depend on both release of excitatory amino acids and oxygen free-radical-mediated membrane lipid peroxidation.

Animals↗
PubMed1993

Increased dose-rate effect in V79-multicellular aggregates (spheroids). Relation to initial DNA lesions and repair.

Survival of exponentially growing V79 monolayer cells was measured after irradiation at low dose-rate (up to 1.1 Gy/h) and at high dose-rate (2.5 Gy/min) and compared to corresponding survival data of V79 spheroid cells. The so-called contact effect, the increased radioresistance of cells irradiated in spheroids, was expressed to a greater extent with low dose-rate exposure. Lesion fixation by hypertonic treatment was more pronounced in spheroid versus monolayer cells and abolished the contact effect. The reduced radiosensitivity of V79 spheroid cells could not be related to a reduced number of initial DNA lesions or a higher capacity to rejoin DNA breaks (measured by neutral elution). These findings suggest that the ratio of lesion repair to fixation/misrepair may differ between cells from spheroids and monolayer culture thus influencing the response of cells to dose-rate changes differentially.

Animals↗
PubMed1993

Effects of non-opioid antitussives on hypoxia-induced electrical changes in rat hippocampal slices: a comparative study with anticonvulsant drugs.

1. The effects of the non-opioid antitussives caramiphen and carbetapentane and of the anticonvulsants 5,5-diphenylhydantoin and MK 801 were tested towards hypoxia-induced electrical changes in rat hippocampal slices. 2. The incidence of appearance of hypoxia-induced epileptiform bursting was significantly decreased (P < 0.05) by carbetapentane (50-100 microM), caramiphen (50-100 microM), 5,5-diphenylhydantoin (25-50 microM), and the glutamate antagonist dizocilpine (MK 801, 25-50 microM). 3. The incidence of reappearance of the CA1 population spike after hypoxia was significantly increased (P < 0.05) by carbentapentane (50-100 microM), caramiphen (50-100 microM), 5,5-diphenylhydantoin (25-50 microM), and MK 801 (25-50 microM). 4. The results suggest a useful role for non-opioid antitussives and some anticonvulsants in the treatment of hypoxia-induced functional disturbances.

Animals↗
PubMed1993

Absence of calcium-induced LTP-like response in the dentate area of seizure-prone gerbils and its relation to parvalbumin in the entorhinal perforant path synapse of this species.

Mongolian gerbils (Meriones unguiculatus) are genetically predisposed to seizures, for which an involvement of hippocampal hyperexcitability and disinhibition has been suggested. The response in vitro of the hippocampal synaptic circuit upon exposure to an elevated extracellular calcium concentration is well known in the rat, and its dependence on inhibitory and excitatory transmission has been thoroughly studied. The purpose of the present investigation was to compare the influence of elevated extracellular calcium on inhibitory and excitatory transmission in the dentate area and the CA1 field of gerbil and rat hippocampal slices. Elevated calcium induced in the CA1 area of both animal species a long-term potentiation (LTP)-like response. Upon calcium exposure in the dentate area a decrease in population spike amplitude occurred in both gerbil and rat slices, indicating a similar degree of synaptic inhibition in the two species. However, in contrast to the effects known in the rat, elevated extracellular calcium failed to enhance the excitatory postsynaptic potential in the gerbil dentate area. This difference may depend on the species-specific, selective presence of the calcium-binding protein parvalbumin in perforant path terminals of the gerbil, which may be relevant to the susceptibility to seizures of this animal species.

Animals↗
PubMed1993

Effects of calcium and paired-pulse stimulation on hypoxia-induced hippocampal electrical changes.

The influence of calcium concentration changes (2 and 4 mM) and of the paired-pulse stimulation (PPS) paradigm on the effects of hypoxia has been investigated in rat hippocampal slices. Because a high calcium concentration (4 mM) facilitates paired-pulse inhibition (PPI) at a 15-ms interpulse interval, the influence of hypoxia-induced effects were tested against calcium-induced PPI. In the PPS, unconditioned response at calcium concentrations of 2 and 4 mM, and 15- or 30-ms interpulse intervals of stimulation, no significant differences were found in the latency to induce a 50% amplitude decrease of the CA1 population spikes during hypoxia. On the contrary, in the conditioned response the latency to induce a 50% amplitude decrease of CA1 population spikes was significantly increased (p < 0.01) at 4 mM calcium, 15-ms interpulse interval with respect to experiments with 2 mM calcium, at 15- or 30-ms interpulse intervals. The data indicate that PPI is strongly affected during the early phases of hypoxia and also suggest that drugs increasing PPI could be successfully used for the treatment of brief anoxic or ischemic functional alterations.

Animals↗
PubMed1993

Diabetes mellitus in Tohon O'odham pregnancies.

OBJECTIVE: To determine the prevalence of diabetes in Tohono O'odham pregnancies, and to assess the efficacy of early prenatal diabetes screening in populations with high rates of diabetes. RESEARCH DESIGN AND METHODS: All Tohono O'odham women receiving prenatal care at the Sells Service Unit who delivered a viable baby in the 5-yr study period were reviewed. RESULTS: Diabetes was confirmed in 97 of 1854 (5.2%) Tohono O'odham pregnancies delivered during the study period. NIDDM antedated pregnancy in 38 (39%) of the diabetic pregnancies. Diabetes was diagnosed for the first time in 59 (61%) of these diabetic pregnancies. The diagnosis was made at or before the 20th gestational wk in 25 of 59 (42%) gestational diabetic women. These 25 women represented 61% of 41 gestational diabetic women who received prenatal care at or before the 20th gestational week. CONCLUSIONS: Our findings indicate that first trimester diabetes screening is justified in this population and may be appropriate in other populations with high rates of diabetes.

Arizona↗