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Biomedical subjects

R Goulet

Publications and source records attributed to R Goulet.

14 recordsLinked to original sources
PubMed2001

Dramatic response of teratoma-associated non--germ-cell cancer with all-trans retinoic acid in a patient with nonseminomatous germ cell tumor.

A patient with nonseminomatous germ cell cancer, treated with standard chemotherapy, subsequently developed a pathologically confirmed metastatic undifferentiated adenocarcinoma (non-germ-cell elements) arising from residual teratoma. Disease was present in both lobes of the liver and was deemed unresectable at the time of presentation. The patient was treated on a National Cancer Institute-sponsored institutional protocol with all-trans retinoic acid. After 60 days of oral therapy at a dose of 150 mg/m2/d (50 mg/m2 three times daily), the patient was found to have complete radiologic resolution of his hepatic metastases. He subsequently underwent surgery and his complete response was pathologically confirmed.

Adult↗
PubMed2000

Asthma and airway hyper-responsiveness in adults who required hospital admission for bronchiolitis in early childhood.

Viral respiratory infections in infancy may contribute to the development of airway hyper-responsiveness (AHR) in childhood but their effects on respiratory function at the adult age are still uncertain. A group of 42 subjects aged 17-35 with a pediatrician-made diagnosis of severe bronchiolitis in infancy (Br) were compared for the presence of asthma and AHR to a control group (C) paired for age and gender, without evidence of lower respiratory disease in infancy. All had a respiratory and environmental questionnaire, allergy skin prick tests, blood eosinophil count, total serum IgE determination and measurements of expiratory flows and airway response to methacholine. In Br and C groups, respectively, 38 and 12% of subjects had a physician-made diagnosis of asthma, 26 and 7% used bronchodilators and 12 and 0% an inhaled corticosteroid; 71 and 67%, respectively, were atopic, 50 and 24% were smokers and 43 and 17% had a first-degree relative with asthma. Mean baseline FEV1 and FEV1/FVC ratio were lower in the Br than in the C group, with 94/103% (P=0.002) and 80/87 (P<0.0001) of the predicted value, respectively. Geometric mean PC20 methacholine was significantly lower in the Br than in the C group 3.9/20.3 mg ml(-1) (P<0.0001). Mean blood eosinophil count and serum IgE levels were similar in both groups (P> 0.05). In conclusion, asthma and AHR were found more frequently in young adults with a past history of bronchiolitis, suggesting that this type of respiratory infection may contribute to altered pulmonary function in adulthood, although it may also represent an early manifestation of asthma. The influence of potential confounding factors, such as familial predisposition and exposure to cigarette smoke on the development of asthma and AHR in the Br group, cannot be excluded.

Adolescent↗
PubMed2000

The effect of screw insertion site and unused drill holes on stability and mode of failure after fixation of basicervical femoral neck fracture.

The intent of this biomechanical study is to characterize the effect of unused drill holes and cannulated screw insertion site on the fixation stability and mode of failure after fixation of basicervical femoral neck fractures. Fourteen matched pairs of embalmed human cadaver femora were sorted into four groups according to the level of screw insertion along the lateral cortex. Screws inserted at higher positions along the lateral cortex afforded higher rigidity, thus decreasing the amount of motion at the fracture site. In addition, higher insertion positions reduced the rate of permanent displacement, thus better maintaining reduction. Although all specimens failed at the neck, post-failure inspection revealed upward translation of the inferior screw head when inserted 20 mm below the lesser trochanter. Unused drill holes and guidepin holes had no observed affect on stability or failure mode.

Biomechanical Phenomena↗
PubMed1998

NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1alpha.

Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-kappaB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF-kappaB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-kappaB in macrophages and endothelial cells. NF-kappaB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-kappaB identified IL-1alpha as the factor responsible for NF-kappaB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1alpha transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1alpha and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.

Breast Neoplasms↗
PubMed1997

Pressure vs flow triggering during pressure support ventilation.

BACKGROUND: Adult mechanical ventilators have traditionally been pressure- or time-triggered. More recently, flow triggering has become available and some adult ventilators allow the choice between pressure or flow triggering. Prior studies have supported the superiority of flow triggering during continuous positive airway pressure, but few have compared pressure and flow triggering during pressure support ventilation (PSV). The purpose of this study was to compare pressure and flow triggering during PSV in adult mechanically ventilated patients. METHODS: The study population consisted of 10 adult patients ventilated with a mechanical ventilator (Nellcor-Puritan-Bennett 7200ae) in the PSV mode. In random order, we compared pressure triggering of -0.5 H2O, pressure triggering -1 cm H2O, flow triggering of 5/2 L/min, and flow triggering 10/3 L/min. Pressure was measured for 5 min at the proximal endotracheal tube using a data acquisition rate of 100 Hz. From the airway pressure signal, trigger pressure (deltaP) was defined as the difference between positive end-expiratory pressure (PEEP) and the maximum negative deflection prior to onset of the triggered breath. Pressure-time product (PTP) was defined as the area produced by the pressure waveform below PEEP during onset of the triggered breath. Trigger time (deltaT) was defined as the time interval below PEEP during onset of the triggered breath. RESULTS: A pressure trigger of -0.5 cm H2O was significantly more sensitive than the other trigger methods for deltaP, PTP, and deltaT (p<0.001). There was also a significant difference between patients for deltaP, deltaT, and PTP for each trigger method (p<0.001). CONCLUSIONS: For this group of patients, flow triggering was not superior to pressure triggering at -0.5 cm H2O during PSV.

Acute Disease↗
PubMed1995

Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth and metastasis in athymic mice.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes constitute promising targets in the development of anticancer therapies. Batimastat ([(4-N-hydroxyamino)-2R-isobutyl-3S-(thienyl-thiomethyl)succinyl]-L- phenyl-alanine-N-methylamide) is one of a new class of agents designed to inhibit MMP activity. PURPOSE: We asked whether batimastat, given as adjuvant therapy after primary tumor resection, could inhibit local-regional tumor regrowth and the formation of lung metastases in a human breast cancer xenograft model. We also explored possible effects of batimastat on breast cancer cell viability and on the accumulation of specific messenger RNAs (mRNAs). METHODS: Human MDA-MB-435 breast cancer cells were treated in vitro for 6 days with batimastat at concentrations ranging from 0.1 to 10.0 microM, and then viable cell counts were performed. The activity of collagenases, directly associated with cultured MDA-MB-435 cells or released into their culture fluids, was assessed by gelatin zymography after 1 and 3 days of batimastat treatment (drug range, 0.2-2.0 microM). Athymic nude mice were given daily intraperitoneal injections of batimastat (30 mg/kg body weight) after resection of MDA-MB-435 primary tumors grown in their mammary fat pads; the volumes of tumor regrowths and the numbers and volumes of lung metastases were calculated; neovascularization in the regrowths was assessed by immunohistochemical analysis with an antibody directed against CD31, an endothelial cell antigen. The effect of batimastat treatment on the accumulation of mRNAs encoding specific MMPs and the tissue inhibitor of metalloproteinases-2 (TIMP-2) in cultured cells, primary tumors, and tumor regrowths was measured by RNA dot blotting and hybridization with complementary probes. Linear regression analysis, Student's t tests, and chi-squared analysis were used to evaluate the data. RESULTS: The viability of cultured MDA-MB-435 cells was not affected by treatment with batimastat; however, measured activities for the 72-kd and 92-kd collagenases released by these cells were reduced after batimastat treatment. Intraperitoneal injection of batimastat significantly inhibited the local-regional regrowth of resected MDA-MB-435 tumors in athymic nude mice (in comparison with control mice, P = .035), and it reduced the incidence (P < .05), number (P = .0001), and total volume (P = .0001) of lung metastases. Batimastat treatment did not affect cellular levels of MMP or TIMP-2 mRNAs. CONCLUSION: Batimastat inhibits human breast cancer regrowth and metastasis in a nude mouse xenograft model. Potential mechanisms for batimastat's inhibitory activity do not include direct cell toxicity or alteration of MMP or TIMP mRNA levels.

Animals↗
PubMed1994

Growing teratoma syndrome after chemotherapy for germ cell tumors of the ovary.

BACKGROUND: The growing teratoma syndrome has been described with regard to gonadal and extragonadal germ cell neoplasms in males, but few cases have been reported in the female population. In this condition, masses that enlarge during or after chemotherapy are found to contain mature teratoma without malignant elements. CASES: Three patients had either persistent or growing masses despite chemotherapy for germ cell malignancies of the ovary. All cases fit the description of the growing teratoma syndrome. The patients were aged 20-22 years. All three patients had immature teratomas before chemotherapy. The stages of disease ranged from Ia to IIIc. All patients had normal tumor markers while their masses showed growth or persistence. All were free of disease 6-31 months after diagnosis. CONCLUSION: Growth or persistence of a tumor after chemotherapy for malignant teratoma does not necessarily imply progression of malignancy, especially if tumor markers are normal. However, these masses should be resected because they may cause obstruction, compression, or displacement of adjacent organs, or undergo sarcomatous degeneration.

Adult↗
PubMed1993

Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone.

The mechanical properties of trabecular bone have been shown to vary significantly with age, anatomic location, and metabolic condition. Efforts towards predicting its behavior have been extensive, and significant relationship between measures of density and mechanical integrity have been reported. Unfortunately, the significant heterogeneity in trabecular bone anisotropy contributes to significant unexplained variance in its strength and modulus when predicted using scalar measures of mass or density. As a result, numerous investigators have attempted to include measures of architecture in an effort to more rigorously investigate potential physiologic optimization strategies, as well as account for the increased fragility associated with advancing age. In our laboratories we have utilized a unique three-dimensional, microcomputed tomography system to measure trabecular plate thickness, trabecular plate separation, trabecular plate number, surface to volume ratio, bone volume fraction, anisotropy, and connectivity in isolated specimens of trabecular bone. The results of these studies demonstrate that in normal bone, more than 80% of the variance in its mechanical behavior can be explained by measures of density and orientation. The independent measures of connectivity and trabecular plate number were found to be significantly correlated with bone volume fraction, suggesting a potential strategy in the formation of trabecular bone. It might be hypothesized, however, that the relationship between bone volume fraction and connectivity may be substantially altered under conditions associated with aging, fragility, or metabolic bone disease. This hypothesis would be consistent with the histologic evidence of reduced connectivity in osteopenic patients.

Adult↗
PubMed1993

Direct calculation of the surface-to-volume ratio for human cancellous bone.

There are many diseases which cause detrimental changes in the trabecular structure of cancellous bone, leading to mechanical failure of the tissue. One approach to understanding the mechanisms of these diseases is to create idealized models that recreate the morphology of the tissue. This paper presents a partial development of such a model. Further histological methods must be developed before a complete definition of morphologically valid models is possible. In a histological section of cancellous bone, the orientation and length of the trabecular surfaces determine how a line drawn across the bone section will intersect the bone-marrow interface. The distribution of the average length between intersections for a set of parallel lines is defined as the mean intercept length distribution. In this paper, the average surface morphology and volume of the average structure of cancellous bone is determined from an examination of the mean intercept length. The average structure of cancellous bone contains a repeated structural element (SE). As a result, the basic bone structure is analogous to a brick wall made from many similar bricks. For a group of 107 specimens, a strong relationship between structural element volume (SE.V) and bone volume fraction (BV/TV) is demonstrated, SE.V = 0.017 kappa (BV/TV)-2.05 mm3, R2 = 0.93, with kappa a model-dependent constant. For the same specimens, the structural element surface (SE.S) showed the relationship, SE.S = 0.144 kappa (BV/TV)-1.35, R2 = 0.92. As a result of the inverse square dependence of structural element volume on bone volume fraction, it is predicted that cancellous bone strength is inversely proportional to structural element volume.

Adult↗
PubMed1991

Early bone changes in experimental osteoarthritis using microscopic computed tomography.

Alterations in trabecular subchondral bone have been measured using a microscopic computed tomography scanner in the guinea pig hind-limb myectomy model of osteoarthritis. These bone changes can be found as early as histologic changes in cartilage. To evaluate the influence of the myectomy on the animals, a gait study was performed. This data reveals an alteration in acceleration at the foot-flat phase of gait in the operated limb only, providing early quantification of the interaction between mechanics and biology.

Animals↗
PubMed1989

Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation.

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.

Adolescent↗
PubMedDate not supplied

Effects of plate location and selection on the stability of midshaft clavicle osteotomies: a biomechanical study.

Operative fixation of midshaft clavicle fractures is controversial with few biomechanical data to assist surgical decision making. The purpose of this 2-phase biomechanical investigation is to report on the effects of plate location and selection on the stability of midshaft clavicle fractures. Thirty matched pairs of human adult formalin-fixed clavicles were used. In the first phase, in which a 3.5-mm reconstruction plate and simulated midshaft transverse clavicle osteotomies were used, we observed the effect of superior plate placement compared with anterior placement on fracture rigidity, construct stiffness, and strength. In the second phase, in which simulated midshaft oblique clavicle osteotomies were repaired on the superior aspect, we compared the fracture rigidity, construct stiffness, and strength of the 3.5-mm reconstruction, 3.5-mm limited contact dynamic compression (LCDC), and 2.7-mm dynamic compression (DC) plates. Intact clavicles were prepared, potted, and tested for axial and torsional stiffness in an Instron test frame equipped with gimbaled fixtures. Clavicles were band-sawed to simulate an osteotomy, repaired, re-mounted on the test frame with shear and opening extensometers placed across the osteotomy site, and then tested to observe axial and torsional fracture rigidity and stiffness. Constructs were then loaded to failure in compression. First-order regressions were used to estimate fracture rigidity (in kilonewtons per millimeter)and retained construct stiffness (in kilonewtons per millimeter), whereas the maximum applied compressive load at collapse or gross deformation determined the failure load. Values for the comparisongroups were tested for significance at the 95% confidence level. In the first phase we found that constructs plated at the superior aspect of the clavicle exhibited significantly greater fracture rigidity and mean retained stiffness than the anterior location (P <.05). In the second phase we found that the torsional fracture rigidity of LCDC-plated constructs significantly exceeded that of the reconstruction and DC plates (P <.05), whereas the axial fracture rigidity of the LCDC-plated constructs significantly exceeded that of the reconstruction plate (P <.05). In retained stiffness the performance of the LCDC-plated constructs significantly exceeded that of the DC plate in torsion (P <.05), whereas in load to failure the LCDC plate withstood significantly more compressive load than the reconstruction plate (P <.05). We concluded that clavicles plated at the superior aspect exhibit significantly greater biomechanical stability than those plated at the anterior aspect. Furthermore, we concluded that the LCDC plate offers significantly greater biomechanical stability than the reconstruction and DC plates.

Aged↗