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A Martinez

Publications and source records attributed to A Martinez.

At least 271 records · Page 15Linked to original sources
PubMed1994

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation systems developed by us acquires prescription images from different sources, including film scanner, and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Humans↗
PubMed1994

Conservative surgery and radiation therapy for infiltrating lobular carcinoma of the breast. The role of preoperative mammograms in guiding treatment.

BACKGROUND: The authors have reviewed their institution's experience with conservative surgery and radiation therapy for early stage breast cancer with the goal of defining the impact of infiltrating lobular histology (ILC) on the local recurrence rate. Also, they have examined the preoperative mammograms of the ILC patients to determine if mammographic features could be used to predict treatment outcome. METHODS: Between January 1, 1980, and December 31, 1987, 402 cases of Stages I and II breast cancer were treated with conservative surgery and radiation therapy (BCT) at William Beaumont Hospital. Each patient had at least an excisional biopsy. Radiation consisted of 45-50 Gy to the entire breast followed by a supplemental boost dose, so that a minimum of 60 Gy was delivered to the tumor bed. Thirty cancers were classified histologically as infiltrating lobular carcinoma (ILC), 346 as infiltrating ductal carcinoma (IDC), and 26 as other. Median follow-up is 60 months. RESULTS: There was no significant difference in 5 year actuarial local recurrence rates between ILC and IDC, 3.3 versus 4.2%, respectively, (P = not significant). Preoperative mammograms were retrospectively reviewed for 29 of the 30 ILC patients. A spiculated opacity was the most common primary mammographic finding (63%), followed by architectural distortion (17%), poorly defined opacity (7%), and negative (7%). Of the patients who had a preoperative primary mammographic finding of a spiculated opacity, 55% underwent reexcision after the initial excisional biopsy, and residual invasive carcinoma was found in 18% of the reexcision specimens. In contrast, of the patients with a primary mammographic finding of an architectural distortion, poorly defined opacity, or negative, 89% underwent reexcision after an initial excisional biopsy, and residual invasive carcinoma was found in 100% of the reexcision specimens. CONCLUSIONS: Infiltrating lobular carcinoma does not have a worse local recurrence rate compared with IDC when each is treated with breast-conserving therapy. The primary finding on preoperative mammograms in patients with ILC may prove to be a useful tool for predicting the likelihood of residual carcinoma in the breast after initial excisional biopsy.

Adult↗
PubMed1994

Regulation by nerve growth factor and protein phosphorylation of Na/K/2Cl cotransport and cell volume in PC12 cells.

PC12 cells possess a bumetanide-sensitive Na/K/2Cl cotransport system similar to that found in other cell types. Between 10-15% of the total 86Rb influx in these cells is mediated by this pathway under normal conditions. The cotransporter has affinities of 16.5 mM for Nao and 0.7 mM for Ko, is absolutely dependent on Clo and is loop diuretic inhibitable (benzmetanide > bumetanide > piretanide > furosemide). The cotransporter can be activated (up to 8-fold) by cell shrinkage or (up to 4-fold) by treatment with the protein phosphatase inhibitors okadaic acid (EC50 approximately 650 nM) or calyculin A (EC50 approximately 8 nM). Cell shrinkage is followed by a bumetanide-sensitive regulatory volume increase as determined in cell sizing experiments. Calyculin A rapidly elevates normal cell volume in a diuretic-inhibitable manner. Cotransport activity and cell volume are also increased by nerve growth factor (NGF) treatment. The effect of NGF on cotransport rate is biphasic, with an initial rapid approximately 2.5-fold increase followed by a prolonged plateau, and is blocked by pretreatment of the cells with K252a (IC50 approximately 30 nM). By contrast, agents that raise cAMP or phorbol esters lead to an inhibition of cotransport, indicating that the NGF effect is not mediated by stimulation of either cAMP-dependent protein kinase or protein kinase C. Long term NGF treatment (> 2 days) leads to neurite formation and a maintained approximately 2-fold increase in cotransport activity. Bumetanide treatment does not affect the ability of cells to extend neurites, nor is the growth rate of cells in normal medium affected by the diuretic. These results suggest that the cotransport system in PC12 cells is acutely regulated by protein phosphorylation and dephosphorylation as well as cell shrinkage and that cotransport activity may be up-regulated during neuronotypic differentiation.

Animals↗
PubMed1994

Improved local control and survival for surgically staged patients with locally advanced prostate cancer treated with up-front low dose rate iridium-192 prostate implantation and external beam irradiation.

PURPOSE: In an effort to improve upon the historically poor local control and survival rates for locally advanced prostate carcinoma, a prospective multidisciplinary clinical trial was initiated using low dose rate Iridium-192 prostate implantation and external beam irradiation. METHODS AND MATERIALS: Between January 1983 and September 1989, 57 patients with newly diagnosed bulky prostatic carcinoma (5 Stage B2, 52 Stage C) were treated at the Mayo Clinic (34 patients) and William Beaumont Hospital (23 patients) with (a) 5 Gy delivered preoperatively in one fraction, (b) pelvic lymphadenectomy with interstitial implantation of the prostate using Iridium-192 seeds via a perineal template to 30-35 Gy, and (c) 30.6 Gy external irradiation to prostate only in 17 fractions. RESULTS: After lymphadenectomy, 30/57 (53%) patients had pathologically confirmed positive lymph nodes or "D1" disease. Thirty-four patients (60%) had Gleason scores > or = 7. Mean age at diagnosis was 63.3 years. Median overall follow-up was 72 months. The 5-year actuarial survival rate was 85% and disease-free survival was 63%. The 5-year survival for patients with negative nodes was 93% and with positive nodes was 79%. The corresponding survival for patients with Gleason scores < or = 6 was 96% and > or = 7 was 78%. Multivariate analysis demonstrated that of all covariates considered, only Gleason score had prognostic significance for disease-free survival (p < 0.05) and no covariates were statistically significant for overall survival. Thirty-nine of the 57 patients had a prostatic re-biopsy performed at 18 months. Pathologically confirmed local control was ultimately achieved in 31/39 (79.5%). There was no difference in survival in patients with positive re-biopsies vs. those with negative results. The 5-year actuarial rate of clinical local control was 94%. Three patients clinically failed locally and 21 demonstrated distant progression. The median time to progression was 34 months. Nineteen percent received some form of hormonal manipulation at the time of their treatment course and an additional 42% were treated with hormones during their follow-up period, primarily after distant failure. The grade 4 rectal ulceration rate decreased to 4.5% with modification of the brachytherapy technique. Three patients experienced grade 4 urinary incontinence and three patients experienced grades 3 or 4 chronic perineal pain. CONCLUSION: These results indicate that bulky prostate carcinoma can be successfully controlled locally by this novel and aggressive approach with moderate toxicity and improved survival.

Adenocarcinoma↗
PubMed1994

Hyperthermic enhancement of high dose-rate irradiation in 9L gliosarcoma cells.

PURPOSE: Long duration-mild temperature hyperthermia has previously been shown to be an effective potentiator of low-dose-rate irradiation. An in vitro investigation was initiated to determine if 41 degrees C hyperthermia could be useful in sensitizing high-dose-rate (HDR) brachytherapy. Experiments were designed to determine the optimal length of heat treatments to be applied with a twice daily 5 Gy times five fraction high-dose-rate protocol. METHODS AND MATERIALS: Rat 9L gliosarcoma cells growing exponentially in flasks were exposed to X-irradiation and 41 degrees C hyperthermia. Irradiation was applied in 5 Gy fractions two times per day to a total dose of 25 Gy. Hyperthermia consisted of combinations of 1 or 4 hr heating before and/or after each of the radiation exposures. In addition, a set of cells was heated continuously at 41 degrees C starting 6 hr before the first fraction and continuing to 4 hr after the 5th fraction. Cell survival was assayed by colony formation. RESULTS: Sensitization of high-dose-rate increased linearly with increasing length of 41 degrees C heating over the entire range of heat exposures applied. Maximum sensitization was produced by continuous heating for 58 hr throughout the entire radiation course. Heating for 4 hr before fractions two through five produced less sensitization to these later fractions than was expected if each heat-radiation fraction had acted independent of the other fractions. CONCLUSION: Continuous 41 degrees C heating eliminated split dose sparing during high-dose-rate. The apparent development of thermotolerance during the course of heat and high-dose-rate resulted in reduced sensitization in the later fractions when 4 hr pre- and/or post-heat were applied. This tolerance was overcome if heat was applied continuously between radiation fractions. The clinical relevance of these in vitro data is that 41 degrees C hyperthermia should be applied for as long as is possible during this type of high-dose-rate protocol. This combined hyperthermia-high-dose-rate treatment may enhance the efficacy of interstitial irradiation in situations such as boost irradiation of high grade glioma.

Animals↗
PubMed1994

The sequence and expression pattern of the Calliphora erythrocephala yolk protein A and B genes.

The yolk protein genes (yps) are expressed in a temporal, tissue- and sex-specific fashion in Drosophila melanogaster. Here we report the sequence of two related genes in Calliphora erythrocephala. The predicted Calliphora yolk protein (YP) sequences are well conserved, especially at the C-terminal end when compared to those of D. melanogaster and Ceratitis capitata. Database searches with the Calliphora yolk protein B (CeYPB) sequence identify the vertebrate lipase similarity reported for the YPs of Drosophila and Ceratitis. Moreover, sequences with identity to divalent ion-binding sites were observed, which colocalized with putative tyrosine sulfation sites. Calliphora oogenesis differs from Drosophila in that it is cyclic in response to a meat feed. The Calliphora yp genes are expressed in the follicle cells of the egg chamber during vitellogenesis, as shown by in situ hybridization, and the yp message levels correlate with YP synthesis. The synthesis of the yp transcripts in ovaries of Calliphora occurs in the same pattern as that for ovarian transcripts in Drosophila. In the carcass, yp transcript levels are correlated with the production of a batch of eggs.

Amino Acid Sequence↗
PubMed1994

"Depressed" mothers' perceptions of their preschool children's vulnerability.

"Depressed" mothers who scored in the depression range on the Beck Depression Inventory when their infants were 3-months-old were asked to complete the Vulnerable Child Scale when their children were preschool age. Depressed versus non-depressed mothers rated their preschool children as being more vulnerable (as did an independent observer) as well as having more behavior problems. The vulnerability ratings were significantly related to infancy stage measures including the POMS (mothers' depressed mood), the infants' behavior ratings and heart rate range during interactions with a nondepressed stranger. These measures of the mothers' and infants' behavior tapped during early infancy may have contributed to the mothers having perceived their children as "vulnerable" during the preschool stage.

Adult↗
PubMed1994

The effects of corticosteroids and thyrotropin-releasing hormone on newborn adaptation and sympathoadrenal mechanisms in preterm sheep.

OBJECTIVES: We examined the effect of prenatal corticosteroids and thyrotropin-releasing hormone on postnatal adaptation and sympathoadrenal function in preterm lambs. STUDY DESIGN: Catheterized fetal lambs received saline solution (n = 6), corticosteroids alone (n = 8), or corticosteroids plus thyrotropin-releasing hormone (n = 6) for 60 hours. The lambs were delivered by cesarean section at a gestational age of 130 +/- 1 days. Ventilatory, cardiovascular, and metabolic responses and plasma catecholamine concentrations were measured for 2 hours after birth. Statistical analysis was performed by use of independent t tests or analysis of variance. RESULTS: Ventilatory function and cardiac contractility were significantly improved in both corticosteroid and corticosteroid plus thyrotropin-releasing hormone animals. Lambs treated with corticosteroid plus thyrotropin-releasing hormone had significantly higher aortic pressure and left ventricular blood pressure than either of the other groups. The postnatal norepinephrine and epinephrine surge was blunted in response to corticosteroid and corticosteroid plus thyrotropin-releasing hormone treatment. There were no differences in metabolic responses among the three groups. CONCLUSIONS: In premature lambs prenatal exposure to corticosteroids and thyrotropin-releasing hormone improves postnatal cardiovascular adaptation more than corticosteroids alone.

Adaptation, Physiological↗
PubMed1994

Platelet-activating factor induces airway mucin release via activation of protein kinase C: evidence for translocation of protein kinase C to membranes.

Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent assay using a monoclonal antibody raised against airway mucin-type glycoproteins. Coincubation of FTEC with PAF (5 microM) and pharmacologic PKC inhibitors, sphingosine, H7, or calphostin C, inhibited PAF-induced mucin secretion at 30 min. The PKC inhibitors produced a concentration-dependent, noncytotoxic inhibition. Exposure of FTEC with the PKC activator phorbol 12-myristate 13-acetate (PMA), failed to increase the release of mucin. Stimulation of FTEC with PAF caused a transient increase of membrane-bound PKC activity after 5 min of stimulation. PMA also induced the translocation of PKC activity from the cytosol to the membrane fraction, which was still present after 15 min of exposure. Determination of the specific PKC isozyme(s) involved in PAF-induced mucin release was performed by immunoblot analysis of the subcellular fractions using a battery of antibodies against various PKC isozymes (anti-PKC alpha, beta, delta, gamma, epsilon, and zeta). We found that PKC zeta (mol wt approximately 70 kD) was a major identifiable PKC isozyme present in the cytosolic fraction of FTEC. Furthermore, PKC zeta isozyme was also found to translocate to the membrane fraction following PAF exposure. Thus, these results demonstrate the crucial role of PKC in the intracellular events that culminate in mucin release following PAF stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Concurrent treatment planning for outpatient high dose rate prostate template implants.

PURPOSE: Since November of 1991, we have treated locally advanced (B2-C) prostate cancer using external beam radiotherapy integrated with outpatient high dose rate interstitial implant boost as part of a Phase II clinical trial. This required (a) rapid, automated planning; (b) incorporation of image data and (c) dose optimization. METHODS AND MATERIALS: A treatment planning system was designed which integrates imaging and needle guidance with source reconstruction and dose display. All components of treatment planning (reconstruction, optimization, dose prescription, dose display) are largely automated. A rectal reference point was defined which was reproducible and easily verified. No pretreatment planning was required. RESULTS: As of November 1992, 83 treatments were delivered using this system. Intra-operative treatment decisions were made possible due to the speed and ease of interpretation of the system. The system has proven satisfactory in the operating room. Rectal doses were calculated for all patients, and ranged from 35-79% of the prescribed dose, with a mean of 58%. The first echelon of a Phase II escalating dose trial has been completed, with 22 patients treated over a period of 1 year. CONCLUSION: Outpatient high dose rate brachytherapy appears to be a practical means of boosting locally advanced prostate cancer patients. Rapid treatment planning is possible incorporating on-line ultrasound images to allow immediate dose optimization to be performed during and after implant placement.

Brachytherapy↗
PubMed1993

Chandelier cells in the hippocampal formation of the rat: the entorhinal area and subicular complex.

In the present study we describe the characteristics of the chandelier cells in the rat entorhinal cortex and subicular complex by using the Golgi method and combined Golgi-electron microscopic techniques. In the entorhinal cortex, chandelier cells were frequently stained in layers II/III. Two types of axonal complexes were noted. One had a preferential horizontal orientation and gave rise to terminals located in the upper portion of layers II/III. The second type of chandelier cell axon was observed in the medial entorhinal area, innervating the entire extent of layers II/III. In the subicular complex, chandelier cells were frequently stained in the parasubiculum, whereas only a few cells were found in the presubiculum. In both subfields, chandelier cell axons were restricted to layers II/III. In the subiculum, most chandelier cells were present in the stratum radiatum, giving rise to a descending axon that branched in the stratum pyramidale. Both the size and morphological features of the chandelier cell terminal portions were found to be region-specific. Electron microscopically, the cell body and dendrites of gold-toned chandelier cells displayed typical features of nonpyramidal cells, such as the presence of nuclear infoldings, symmetric and asymmetric synapses on the cell body, and moderate numbers of axon terminals covering the smooth dendritic surface. Five gold-toned chandelier cell axonal complexes were analyzed at the fine structural level. In all parahippocampal regions, gold-labeled axon terminals formed symmetric synaptic contacts with axon initial segments. Our results demonstrate the presence, morphological characteristics, and target selectivity of identified chandelier cells in the parahippocampal region of the rat. Together with previous data, these results suggest a wide distribution of this specialized type of cortical interneuron and indicate that it is a constant and essential component of inhibitory circuits in the cerebral cortex. The possible significance of chandelier cells for the circuits linking several subfields of the hippocampal formation is discussed.

Animals↗
PubMed1993

The use of iodine-125 seeds as a substitute for iridium-192 seeds in temporary interstitial breast implants.

PURPOSE: We have previously reported that the use of iodine-125 seeds in temporary plastic tube interstitial implants may be more advantageous than iridium-192 seeds due to less patient and personnel radiation exposure, reduced shielding requirements, and significant dosimetric advantages. The impact of this isotope on the rate of local control and cosmetic outcome in patients with early stage breast cancer treated with interstitial implants for their irradiation "boost" remains to be defined. METHODS AND MATERIALS: We reviewed the treatment outcome of 402 consecutive cases of Stage I and II breast cancer undergoing breast conserving therapy between 1/1/80 and 12/31/87. All patients underwent excisional biopsy and received 45-50 Gy to the entire breast followed by a boost to the tumor bed using either electrons (104 patients), photons (15 patients), or an interstitial implant with either iridium-192 (197 patients) or iodine-125 (86 patients) to at least 60 Gy. Iodine-125 implants were primarily performed in patients with significant risk factors for local recurrence (71%) or in patients with large breasts (17%). Local tumor control and cosmetic outcome were assessed and contrasted between patients boosted with each modality. RESULTS: With a median follow-up of 59.3 months, 18 (4.5%) patients developed a recurrence of the tumor in the treated breast (4.4% 5-year actuarial rate). No statistically significant differences in the 5-year actuarial rate of local recurrence were noted between patients boosted with either iodine-125 (3.0%), iridium-192 (3.8%), electrons (5.4%), or photons (0%). Likewise, no significant differences in the percentage of patients obtaining good/excellent cosmetic results were noted between iodine-125 (93%), iridium-192 (88%), electrons (90%), or photons (82%). CONCLUSION: We conclude that patients with Stage I and II breast cancer undergoing breast conserving therapy and judged to be candidates for boosts with interstitial implants can be effectively treated with iodine-125 seeds. Use of this isotope results in less patient and personnel irradiation exposure and a better dose distribution than iridium-192, since dose optimization can be routinely employed. Overall, local control and cosmetic outcome have been excellent and are similar to either iridium-192, electrons, or photons.

Brachytherapy↗
PubMed1993

Sensitivity of human cells to mild hyperthermia.

The cytotoxic effects of short duration, high temperature, and long duration, low temperature hyperthermia were determined in human cells growing in culture. The human tumor cell lines A549 (lung carcinoma), WiDr (colon carcinoma), and U87MG (glioblastoma) were used. In addition, a normal human lung fibroblast cell type 18Lu was used. Sensitivity to direct cell killing was measured at 41, 43, and 45 degrees C. Heat induced perturbations of cell cycle and proliferation were also analyzed. The results obtained on sensitivity of the above human cell lines at 43 and 45 degrees C are similar to those of the previous work of others in that the human cell lines were observed to be relatively resistant to thermal killing at 43 or 45 degrees C, when compared to heat sensitive rodent cell lines. The comparison is important because most prior hyperthermic research has been performed with rodent cells and clinical protocols have been designed with the use of rodent data. In contrast to the 43 degrees C response, most of the human cells we tested were killed by 41 degrees C heating to an extent greater than that observed for rodent cells. The heat sensitivities of the four different human cell lines varied widely. This appeared to be due to differences in both intrinsic heat sensitivity and tolerance development. During 41 degrees C heating, human cells did not proliferate and cell cycle perturbations developed but did not correlate with sensitivity to killing. Our heat sensitivity measurements point out the shortcomings of using data derived from rodent systems to predict clinical outcome of hyperthermia therapy.

Animals↗